T icity experiments performed in vitro and in vivo using organic and inorganic metal compounds,

(1)

JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY Volume 3, Number 6, 1984

Mary Ann Liebert, Inc., Publishers

A

Survey

of

Metal-induced Mutagenicity

in Vitro and in Vivo

K. HANSEN' and R.M. STERN'

ABSTRACT

A survey of the literature shows that organic and inorganic compounds of

53 metals have

been assayed for genotoxic effects in vitro and in vivo. It is falund that there are great

variations in the response obtained with different test systems and that a wide range of

compounds of the different metals is positive in at least one of the short-term tests. Some

of the variation observed could be due to differences in uptake mechanisms. This effect

plus the wide variation in the quantity and quality of the data ]prevents any direct com-

parison of in vitro activity with in vivo potency of the various imetallic species.

INTRODUCTION

HE INTERNATIONAL literature has been surveyed in an attempt to correlate the results of genotox-

T

icity experiments performed in vitro and in vivo using organic and inorganic metal compounds, with known carcinogenic effects of metals in man. Compounds of

53

metallic elements are reported to have been tested for genotoxic effects (Table l), but the number of experiments for which the individual metals have been tested is found to vary widely, e.g., chromium has been assayed in more than

300

individual experiments, where

as

beryllium has been tested in only

24

cases.

For

those 5 to

10

metals with significant data bases, e.g., nickel and chromium, the prevalence of positive data agrees with the epidemiological evidence, although the wide range of in vivo and in vitro potency still prevents resolution of questions of compound specificity. For the many remaining metals with relatively little available data, it is impossible to determine if there is a preponderance of positive

or

negative results

or

to make comparisons between them. The main purpose of this survey is to review the present status of the short-term screening data base for metals and to identify neglected or con- troversial areas deserving of further study. It is also intended for use as a resource in the process of estimating potential human risk.

SURVEY OF THE METALS

A large number of test systems have been used for the study of metals. These systems have been grouped into the following

16

categories:

1 . Infidelity of DNA synthesis in vitro

2. DNA damage in prokaryotes 3 . DNA repair in prokaryotes 4. Ames Salmonella-microsome test

'Danish National Institute of Occupational Health, 2900 Hellerup, Denmark, *The Danish Welding Institute, 2600 Glostrup, Denmark.

(2)

w CQ h,

Lanthanides1

;;

I I

I 1

f'

Actinides

90*

Th

Pa

Np

Pu

la

2a

36 4b

5b

6b

7b

8 Ib

2b

3a

4a

5a

6a

7a

0

1

2 H

He

3*

4*

5

6

7

8

9

10 Li

Be

BCNOFNe

11*

12*

13*

14*

IS

16

17

18 Na

Mg

A1

Si

P

S

C1

Ar

-

z

19*

20*

21 22*

23*

24*

25*

26*

27*

28*

29*

30*

31*

32 33*

34*

35

36 ?i

3

87

88 89++

104

105

106

2 K

Ca

Sc

Ti

V

Cr

Mn

Fe

Co

Ni

Cu

Zn

Ga

Ge

As

Se

Br

Kr

%

z

37*

38*

39*

40*

41*

42*

43 44*

45*

46*

47*

48*

49*

SO*

51*

52*

53

54 Rb

Sr

Y

Zr

Nb

Mo

Tc

Ru

Rh

Pd

Ag

Cd

In

Sn

Sb

Te

I

Xe

55*

56*

**57*'**

72 73*

74*

75 76*

77*

78*

79*

80*

81*

82*

83*

84

85

86 Cs

Ba

La

Hf

Ta

W

Re

0s

Ir

Pt

Au

Hg

T1

Pb

Bi

Po

At

Rn

Fr

Ra

Ac

*At least one compound of the metal has been tested.

63*

Eu

95 Am

64 65*

66

67 68*

69

70

71

Gd

Tb

Dy

Ho

Er

Tm

Yb

Lu

96

97

98

99

100

101

102

103 Cm

Bk

Cf

Es

Fm

Md

No

Lr

(3)

METAL-INDUCED MUTAGENICITY

5.

Mutation tests using

Escherichia coli

6.

Eukaryotic microorganisms

7 .

DNA damage and inhibition of DNA synthesis in mammalian cells

8. DNA repair tests in mammalian cells

9. Chromosome aberrations (CA) in mammalian cells in vitro

10.

Sister chromatid exchanges (SCE) in mammalian cells in vitro

1 1.

Mutation in mammalian cells in vitro

12.

Mammalian celI transformation

13.

Drosophila

14.

In vivo mammalian mutations and cytogenetics

15.

Higher plants

16.

Others

The principles of the systems and some examples of the type of cells and methods used in these

categories are briefly described in Appendix

1 . The metals and metalloids that have been tested are

listed alphabetically according to their English names in separate sections for each of the elements in

Appendix

2.

The literature survey has disclosed that a wide range of salts and other compounds has been

studied, including organic and inorganic compounds of metal ions in various oxidation states. Usu-

ally the chemical formulas have been given, and these are used to identify the compounds listed. In

some cases, especially for complex substances, the chemical formulas have not been disclosed or

defined, and the substances assayed are listed by name only.

Inorganic compounds are listed in subgroups in the order of the oxidation state of the appropriate

metal ion, followed by groups of inorganic salts, and finally complex compounds. The results from

mutagenicity testing of some nonmetallic inorganic compounds are included as well.

Dividing the many test systems into the 16 groups permits a rapid comparison of the extent of the

database for both metallic ions and individual compounds, a limited overview of which can be seen

in Table

2,

for those metals for which there might be interest in ascertaining human risk. A positive

sign indicates at least one positive result regardless of the number

of negatives, and a negative sign

indicates the absence

of

positive results.

In order to increase the utility

of

this survey, an attempt has been made to evaluate the data in

each of the original articles. Positive results are classified into three categories according to the

degree to which the information is quantitative:

(1)

data that merely indicate positive response at

some dose level, (2) data that permit a comparison of the positive response with a negative control,

(3)

data that indicate a dose-response relationship. Negative test results regardless of quality are

separately indicated. Some results are felt to be equivocal and are so indicated. No attempt has been

made to evaluate the laboratory practice used in the test procedures

ais

reported.

In the absence of comments to the contrary, the original papers have been referred to in preparing

the listing, and review articles have been used only as a source of additional references. Limited use

has been made of the available data bases such as BLAISE, TOX-LINE, and the abstracting jour-

nals. The literature has been examined through to the end of

1982.

In

order to faciliate identification of references, entries in Appendix

2

consist of a number that

corresponds to an entry in the Reference list.

DISCUSSION

An impression of the current state of genotoxic screening of the metals can be obtained from ex-

amination of Tables 1 and

2.

Table

1 shows that inorganic complexes of a relatively large fraction of

the common elements up to atomic number 83 in the Periodic Table have been examined in at least

one assay. From Table

2

it can be seen that only a relatively few elements have been examined in a

significant number

of

the 16 groups of test systems. It cannot be determined however, to what extent

the metallic compounds have been investigated for their specific activity without detailed examina-

tions of Table

3

(Appendix 2).

(4)

TABLE

2. SOME

METALS

POSITIVE

IN

SHORT-TERM

ASSAYS

Sb

As

Be

Cd

Cs

Cr

Co

Cu

Fe

Pb

Mn

Hg

Mo

Ni

Pt

Rh

Se

Ag

Te

TI

V

Zn

w 00 P ~~

1. Infidelity

of

DNA

synthesis

-++

+++++++

+

-+

-

2. DNA

damage

in

prokaryotes

+

-

+

-

+

-

+

in

vitro

X

3. DNA

repair

in

prokaryotes

+

4. Mutation

in

S. typhimurium

- -

-

+-++----

-++

+-+--+

9 -

-+

-++

---

2:

!2

5.

Mutation

in

E. coli

6. Eukaryotic

microorganisms

-

++

-+

7. DNA

damage

in

mammalian

8. DNA

repair

in

mammalian

cells

+

U

9. CA

in

mammalian

cells

in

vitro

+++

+-

-+++

++

+

++-+

10. +-

++++

++

-

11. Mutation

in

mammalian

cells

+++

12b.

Enhancement

of

viral

+-+

--

-+

z

+

$

++

+

3 z

cells

+

+++

++

++-

+

-+--

SCE

in

mammalian

cells

in

vitro

12a.

Morphological

transformation

+++

++?

-+?

++

-

transformation

++++

++++++++++

+

13. Drosophila

+

-+

+

14.

Mammalian

in

vivo

assays

++

+

15. Assays

using

higher

plants

-+++++++++++

++

3

+

-

(5)

METAL-INDUCED MUTAGENICITY

Since a few of the metals (chromium, nickel, arsenic, cadmium, and beryllium) are strongly

suspected human carcinogens based on standard criteria, it might be expected that they have re-

ceived a significant amount of attention. This is, in fact, true with the notable exception

of

beryllium, which for unknown reasons has been little studied. For chromium, nickel, and arsenic,

the preponderance of positive test results as found in many systems is as imight be expected if there is

a connection between mutagenicity, genotoxicity, and carcinogenicity. 'The question of the use of in

vitro studies to predict in vivo risk cannot be resolved for cadmium because of a mixture of positive

and negative results across compounds and systems for this metallic ion.

For some of the metals, e.g., chromium, selenium, and arsenic, the geiiotoxic potency depends on

the oxidation state of the metal ion. Inorganic Cr

111

is inactive in test systems using intact cells,

whereas Cr VI is positive in

all

these assays. Compounds of trivalent arsenic are more active than the

pentavalent compounds in chromosome aberrations tests, and Se(1V) compounds seem to be more

potent than the Se(V1) compounds. The results obtained with selenium are especially difficult to in-

terpret, as some of them show antigenotoxic effects whereby selenium diminishes the mutagenicity

induced by other agents. Similar conflicting results are seen in animal cancer studies.

Some of the Cr

111

complexes that are carrying stable aromatic amines as ligands show a

mutagenic effect in prokaryotes. Others, such as the complexes of platinum, show a mutagenic re-

sponse depending on the configuration of the complex, e.g., cisplatin tliaminedichloride is a more

potent mutagen than the transconfiguration.

Very few attempts have been made to elucidate the question of synergistic or antagonistic effects

of two or more metals in short-term bioassay. It has been shown that manganese dust reduces cell

transformation induced by nickel subsulfide, that arsenite and

UV

light act synergistically in

mutagenicity and DNA repair assays, and that NiSO, and benzo(a)pyrene show a synergistic effect

in a cell transformation assay using primary Syrian hamster embryo cells.

Some of the variation observed in the results

of the bioassays of different metal complexes could

be due to differences in bioavailability (i.e., uptake mechanisms) rather than reflecting (molar)

genotoxic potency. The extent to which a compound at a given dose is taken up by the biological

system and is able to reach the target molecules depends, among other things, on the nature of the

uptake mechanism and on the (intracellular) reactivity of the compound in the actual surroundings,

e.g., the cell cytoplasm. Insoluble particles are incorporated into cells by different mechanisms than

are the soluble salts, whereas the complex organic compounds may reach the target organelles by yet

other pathways. Test systems using prokaryotes, yeast cells, mammalian cells or entire animals will

each exhibit a wide variation in the extent and rate at which they pick up those various metal com-

pounds that demand different uptake mechanisms.

Thus it may be misleading to compare results of different compounds administered at the same

dose in a given system, or the same compound as administered in different systems. Although the

data base is seen to still be very incomplete, the above arguments indicate that when attempting to

complete the survey

of metals, care should be taken in choosing both in vitro and in vivo short-term

test systems that are relevant to the materials used.

Short-term bioassay might be used to determine the presence or extent of risk of human exposure

to

the metals and their inorganic and organic complexes. Based on examination of the available

data, the tentative conclusion reached is that a summing up of positive and negative test results ob-

tained for each of the metallic compounds cannot be used to predict the potential human risk in-

volved with, for example, occupational exposure to metals. What can be done is to identify which

particular substances, e.g., found in specific occupational exposures, behave in vitro in ways that are

consistent with those for other, similar substances for which there exists a knowledge of eventual

human risk, thereby permitting a transfer of risk assessments from one substance to another or from

exposures in one industry to another.

An effort should be made to extend the use of the data base for the assessment of human risk. It is

undoubtably worthwhile to fill in certain gaps through the systematic use of additional test systems

for specific compounds and additional compounds with specific systems so as to develop further

understanding

of

the mechanisms controlling biological activity. Without this understanding, it may

(6)

in many cases be necessary to treat each metallic complex as a separate entity, since there is such a

wide range of the physical and chemical properties of otherwise related compounds (such as the

ox-

ides). The short-term bioassay data base of inorganic substances does not provide the same tools for

risk estimation as are available for organic chemicals.

APPENDIX 1: TEST SYSTEMS

The test systems have been divided into 16 groups consisting of in vivo and in vitro assays using

prokaryotes and eukaryotes and with different genetic endpoints.

A brief description of each of

the

groups is presented, with references on the principles and methods of the test systems. Most of the

references are found in a few well-known books and in the reports

of the US EPA Gene Tox Pro-

gram as listed in the Bibliogrophy. However, for those of the test systems not described therein, the

reader is referred to the actual papers used in the metals survey. Apart from the references cited

below a description and an evaluation

of screening assays can be found in IARC, 1980.

Group I . Infidelity

of

DNA Synthesis

In

Vitro

The test systems are based on cell-free DNA synthesis in which the incorporation of noncomple-

ment nucleotides is measured by radioactive labeling. In one test system an isolated viral DNA

polymerase incorporates radioactive-labeled nucleotides in a synthetic DNA template

of restricted

base composition. The test substances are added together with the labeled nucleotides, and the fre-

quency

of

errors is measured.(’0) In another procedure, the reversion frequency from mutant to

wild-type viral DNA is measured.(56)

Group 2. DNA Damage in Prokaryotes

1. Differential killing of

Bacillus subfilis

(rec-assay)

2. Differential killing of

Escherichia

coli

(Pol A-/Pol

A’)

A nonspecific DNA damaging effect in prokaryotic cells is detected by differential killing. The

prokaryotes deficient in DNA repair capacity are more sensitive to DNA-damaging agents than are

the wild-type prokaryotes, (De Serres and Ashby, 1981, Chap. 12, 13, and

14;

Leifer et al. 1981,

Gene Tox Program.)

Group 3. DNA Repair in Prokaryotes

I .

Inhibition of excision repair in

E. coli

2.

Inhibition of SOS repair in

E. coli

Inhibition of the error-free excision repair of pyrimidine dimers after radiation exposure results in

an enhancement of the mutation frequency of

E. coli.

( 4 6 )

Inhibition of the postreplication repair

pathway, the error-prone

SOS

repair causing a decrease in, e.g., UV-induced mutations in certain

E. coli

strains (lacking excision repair capacity).‘”)

Group 4. Ames Salmonella-Microsome Test

In the Ames Salmonella-microsome assay the number

of

reversed mutations in

Salmonella

typhimurium

from histidine requirement to histidine independence expresses the mutagenic activity

of the test compound. The

Salmonella

strains most commonly used are TA 1535, TA 1537, TA 1538,

TA 98, and TA 100 in different test procedures with and without metabolic activation (S-9 mix), see

group 5 (Brusick, 1981, Chap. 9, prot. 1; Stich and San, 1981, Chap. 11, 12).

Group

5. Mutation Tests Using E. coli

E. coli

is used for detection of mutagenic activity in the same way as

S. fyphimurium.

Different

strains of

E. coli

detect forward as well as reversed mutations. Three essentially different test pro-

(7)

METAL-INDUCED MUTAGENICITY

cedures are used- the qualitative spot test, in which the test compound iis placed in the middle of the

surface of the agar, the quantitative plate incorporation assay in which the test compound is mixed

with the bacteria in the agar, and the sensitive fluctuation test in whichi the entire procedure is per-

formed in liquid medium. (De Serres and Ashby,

1981,

Chap.

36, 37;

Brusick,

1980,

Gene Tox Pro-

gram).

Group 6. Eukaryotic Mircoorganisms

1 .

Saccharomyces cerevisiae:

mutation, gene conversion, and mitotic crossing over, inhibition of

2.

Schizosaccharomyces pompe:

forward mutation and gene conversion

S. cerevisiae

is

the most frequently used eukaryotic microorganism. Point mutations as well as

chromosome aberrations can be detected (Brusick,

1980,

Chap.

9,

prot.

2,

3,

4; De Serres and

Ashby,

1981,

Chap.

39;

Stich and San,

1981,

Chap.

15).

spontaneous mutation

Group 7. DNA Damage and Inhibition

of

DNA Synthesis in Mammalian Cells

1 .

Inhibition of DNA synthesis in BHK cells, human lymphocytes, CHO cells, and HeLa cells

2.

DNA-protein crosslinks, DNA-DNA crosslinks in

V-79

cells and in CHO cells

3. DNA strand breaks- alkaline elution and sucrose gradient in CHO cells and human fibroblasts

Several test systems detect a nonspecific DNA-damaging effect on mammalian cells. DNA strand

breaks are detected by an alkaline elution technique

or by differential centrifugation (sucrose gra-

dient). Detection of DNA-DNA crosslinks and DNA-protein crosslinks can also be obtained by

alkaline elution. Inhibition of DNA synthesis in mammalian cells is detected by measureing the up-

take rate of labeled thymidine. (Stich and San,

1981,

Chap. 5,

6, 9).

Group 8. DNA Repair Tests in Mammalian Cells

1.

Unscheduled DNA synthesis in mouse cells, human fibroblasts, human lymphocytes, and

2.

Interruption of dark repair mechanism in human lymphocytes

The effect of the test compound on DNA repair mechanisms in manimalian cells is investigated by

measuring unscheduled DNA synthesis (UDS) or DNA repair synthesis. The uptake of radioactive-

labeled thymidine in cells not in the S period indicates that one or more of the repair systems are

working. (Stich and San,

1981,

Chap. 7; Brusick,

1980,

Chap.

9,

prot.

9, 10;

Larsen,

1982,

Gene Tox

Program).

CHO cells

Group 9. Chromosome Aberrations in Mammalian Cells In Ktro

1 .

Chromosome aberrations in C3H mouse cells, hamster embryo cells, CHO cells, human lym-

phocytes, human fibroblasts,

V-79

cells, bone marrow cells from mice, and Balb//c 3T3 cells

A number of cell cultures including primary cells, established cell lines, and human cells have been

used. The genotoxic endpoints under consideration are the morphological stable rearrangements or

exchanges of the chromosomes as well as the unstable breaks and gaps.

Group

10,

SCE

in Mammalian Cells in Vitro

1 .

CHO cells, human lymphocytes, human fibroblasts, and xeroderma pigmentosum cells

Sister chromatid exchanges (SCE) are a result

of

genetic damage at the chromosomal level. When

DNA

lesions are replicated during the S period, exchanges between

t w o

daughter molecules often

occur. On the cellular level this is seen as an exchange between two sister chromatids

in the meta-

phase (Stich and San,

1981,

Chap. 20; De Serres and Ashby,

1981,

Chap.

49;

Latt et al.

1981,

Gene

Tox Program).

(8)

Group

11. Mutation

in

Mammalian Cells

In

Vitro

1. V-79, CHO, C3H cells in the HGPRTI8azag mutation assay

2. CHO/ouabain-resistant mutations

3. L5178Y/TK+’- mutation assay

Point mutation tests in mammalian cells are predominantly done on cell lines V-79, CHO,

L5178Y. The L5178Y system detects the frequency

of forward mutation in the thymidine kinase

locus from TK-’+ to TK+. In the HGPRT system the mutant cells show a resistance towards

8-azaguanine and dthioguanine that is caused by a blocked or altered HGPRT metabolic pathway.

In much the same way, the Na/KATPase pathway can be altered by mutations and the cells become

resistant toward ouabain (Bradley et al., 1981, Gene Tox Program; De Serres and Ashby, 1981,

Chap. 53,

5 5 ; Hsie et al., 1981, Gene Tox Program).

Group 12. Mammalian Cell Transformation

1. SHE, CHO, BHK-21, and Balb/C-3T3 cells

2. Enhancement of virus-induced transformation: HEC cells

+

SA 7-virus, human diploid cells

Different established cell lines and primary hamster embryo cells have been used to detect the

transforming effect of metal compounds. The criterion for transformation is morphological changes

of cell colonies, such as piling-up and a crisscross growth pattern. Measuring the enhancement of

virus-induced transformation is also used as a transformation assay (Stich and San, 1981, Chap. 29,

31; De Serres and Ashby, 1981, Chap. 58, 59; Brusick et al., 1980, Chap. 9, prot. 11).

+

leukosis virus

Group 13. Drosophila

1. Sex-linked recessive lethals

2. Dominant lethals

The X-chromosomal recessive lethals include forward mutations, deletions, and structural rear-

rangements, and approximately 20%

of

the entire genome is covered by this recessive lethals tests. A

dominant lethal mutation in a gamete is considered to be the result of chromosome breaks, but also

nondisjunction can lead to dominant lethality (Brusick, 1980, Chap. 9, prot. 21; Stich and San,

1981, Chap. 34; De Serres and Ashby, 1981, Chap. 61).

Group 14.

In

Vivo Mammalian Mutations and Cytogenetics

1. Chromosome aberrations in bone marrow cells of rat, hamster, and mouse, spermatocytes in

mouse, and oocytes in mouse

2.

Dominant lethals in mouse and rat

3.

SCE in bone marrow cells from mouse and hamster

4. Mouse spot test

5.

Sperm abnormality in mouse

Mammalian tests in vivo are a mixed group of asssays using mainly mice, rats, and hamsters. The

animals exposed to metal salts are examined for chromosome aberrations and SCEs in somatic as

well as germ cells, dominant lethals (germ cell damage), and spots in mice (mutations in genes for fur

color). In the micronucleus test, chromosome breaks

in

bone marrow cells in treated animals can be

counted, since after cell division the daughter cells contain the displaced fragments of chromosomes

as a micronucleus in the cytoplasm (Brusick, 1980, Chap. 9, prot. 14, 16, 17, 18; De Serres and

Ashby, 1981, Chap.

64,

66,

67, 69; Stich and San, 1981, Chap. 21).

Group

15. Higher Plants

1. Mutations and chromosome breaks in

Pisum sativa.

2. Abnormal divisions and chromosome aberrations in

Vicia

faba

(9)

METAL-INDUCED MUTAGENICITY

3. Spindle disturbances and colchicine mitosis in

Allium cepa

4. Mutations in

Crepis capillaris

Root tip cells from

Vicia faba

(broad bean),

Allium cepa

(common, onion),

Pisum sativa

(pea),

Crepis capi/laris

(Hawk's beard) have been exposed to metal salts and examined for induced muta-

tions, chromosome aberrations and abnormal cell divisions (Stich and San, 1981, Chap. 18; Con-

stantin, 1982, Gene Tox Program).

Group 16. Others

1.

Abnormal mitosis in muscle cells(6)

2. Abnormal chick m y o b l a ~ t s ( ~ ~ )

3. Inhibition of mutation in

Bacillus subtilisiS1)

4.

Mutation in

Micrococcus a ~ r e u s ' ~ ~ )

5.

Stimulating of initiating of RNA synthesis on conditions where overall RNA synthesis is

6.

Inhibition of mitochondria1 protein synthesis('*)

7.

Mutation in algae(Ioo

17')

8.

Mutation in bacteriophage T4(125.170

lS6)

9. Effect on DNA in

B. subtilis(161)

inhibited(67)

10. Mitotic spindle disturbances in mouse fibroblasts(16')

1

1. Host-mediated assay:

mouse-Salmonella typhimurium, mouse-Serratia marcescens'

196)

In this mixed group of assays, bacterial systems other than those previously mentioned are found.

well as host-mediated muta-

Assays measuring the inhibition

of

DNA, RNA, or protein synthesis

tion tests using mice and microorganisms are included (Brusick, 1980, Chap. 9, prot. 12).

APPENDIX

2:

SURVEY

OF THE METALS

This is a complete listing of the short-term bioassay of metals, where the test systems are grouped

in the

16

categories described in Appendix 1. Each test result (a chemical substance in a specific

mutagenicity assay) is represented by a number that refers to an entry in REFERENCES. Negative

test results are indicated by brackets around the entry number. Entry numbers without brackets are

used to indicate a positive result as reported by the author: Such results of a qualitative nature are

marked with a single underlining, whereas published quantitative data are indicated with two

underlinings. In those cases where it is felt that the data establish a dose-response

(or

dose-effect)

relationship, the citation is marked with three underlinings.

(To avoid confusion, single-digit cita-

tions appear as 5, -x-,

-x-,

two digits citations appear as

g ,

xx-,

x&-,

and three digit citations as

q,

gx,

xxx).

A question mark indicates that the published result is thought to be equivocal. Addi-

tional comments on test results have been placed in the right column of the tables. No attempt has

been made to evaluate the test procedures as reported.

List of Abbreviations Used in Table

3

8

azag

Balb/c 3Tc cells

BHK-21 cells

CA

C3H/lOT 1/2 cells

CHO cells

E. coli

HEC

or

SHE

HGPRT

L5

178Y

cells

S .

typhimurium

SCE

V-79 cells

8-azaguanine resistance

Mouse fetal cell line

Baby hamster kidney cell line

Chromosome aberrations

Mouse embryo cell line

Chinese hamster ovary cell line

Escherichia coli

Primary Syrian hamster embryo cells

Hypoxanthine-guanine phosphoribtosyl transferase

Mouse lymphoma cell line

Salmonella typhimurium

Sister chromatid exchange

Chinese hamster lung cell line

(10)

TABLE

3. SURVEY

Infideliiy D N A D N A

o f D N A D N A D N A Mutaiions Muralions Eukaryolic Damage in Repnir in

Synthesis Damage in Repnir in in S. in Micro- Mnmmnlinn Mammolian

M e l d in Viiro Prokaryoies Proknryoles typhimurium E. coli organisms Cells Cells

Sb/A ntimony SbIII SbCL SbiO, SbCI, WSb04 Sb(CHSO0)i SbNa tartrate A s / A rsenic As(II1) ASiO3 AsCL KAsOi NaAs02 3AsOs R,AsO(OH) BulAsO(OH) Ph,AsO(OH) M ~ A S O ( O H ) ~ Pr"AsO(OH), (pNH2CsH,)iASO(OH) CHICHCHzAsO(OH)~ Bu"AsO(OH)~ CH,AsO,Ca CH,AsO(OH)ONa CH,AsO(ONa), CH,AsO,Fe NHl(CH2)3AsO(OH)~ RNH(CHi),ASO(OH)i CH,(CHi),NH&(H,OJ MelAsSCH2CH(NH2)COOH C I ~ H ~ ~ A S N ~ O S C,H,AsO(OH)2

3 90

(11)

METAL-INDUCED MUTAGENICITY

OF THE

METALS

SCE in Mutolions M u / . ond

C A in Mummulion in Cell C A in

Mammoliun Cells Mummulion Truns- Mommuliun Higher

Cells in Vilro Cells formation Drosophila in Vivo Plunis Orher Comments

147' (1 76)

'

(1

83)184

169, 126

Dominant lethal

46

Co-mutagen with

91

UV-light

41, 189,

6Q

Mutation in 169' hQ-(4l) mammalian cells 172

42

Significantly higher

activity with trivalent compounds than with pentavalent compounds _-- 147 Review

__- 167 Spindle disturbances

(l89),& in mouse fibroblasts

_-- 174 Eukaryotic micro- R = methyl or ethyl organisms 167' Bu = butyl (1617) Ph = phenyl Pr' = propyl (174)' (174)' 167 147' 167'

391

(12)

TABLE

3

~ ~~

Infideliry D N A D N A

o f D N A D N A D N A Mutations Mutarions Eukaryotrc Damage in Repair in

Synthesis Damage in Repair in in S . in Micro- Mammalian Mammaliar,

Metal in Virro Prokaryores Prokaryotes typhirnurium E. coll organisms Cells Cells

AdArsenic OOCsHjCHzAsO(OH)2 CsH5(CHz)iASO(OWz C I C ~ H ~ A S O ~ NOzCsHaASO, CH,CsH4As03 Acetylarsan Arsenic dimethyl thiocarbamate CH,CICc,H,ASO, Ba/Barium Ba" BaCI, Ba(N0A Ba(CH3C00)2 Be/Beryllium BeCI2 Bi/Bismuth BiC1, Bi(NO,),? 4BiN03(OH), Bi,O, Ca/Calcium Ca" CaCI, Ce/Cerium CeC1, Ce(N0A CdCesium cs2co3 CSCl CsNO, cs2so4 CSCI, CS(NO~), CS,(SO4)3 CHCsO, 182 (182) (182) (79) (79)

392

(13)

METAL-INDUCED MUTAGENICITY

(CONT.)

~~ ~

SCE in Muralions M u r . and

C A in Mammalian in Cell C A in

Mammalran Cells Mammalian Trans- Mammalian Higher

Cells in Vilro Cells formalion Drosophila in Vrvo Planrs Olhfv- Cornnienrs

147l 147' 147l 147'

___

179

82-

302 (183)184 168 Review

212

Enhancement of _ _ _ EMS-induced CA in

183,184 barley root tips

2 ! l

(1 83) 184 (302,297) (57)183 183,184

393

(14)

TABLE

3.

Infidelify DNA D N A

of D N A D N A D N A Mutations Muralions Eukaryotic Damage in Repair in

Synthesis Damage in Repair in in S. in Micro- Mammalian Mammalian

Metal in Vitro Prokaryotes Prokaryotes fyphimurium E. coli organisms Cells Cells

Cd/Cadmium Cd Cd'* CdC1, CdS CdSO, Cd(CH3COO)z Cd-serum 118,280

3

94

(15)

METAL-INDUCED MUTAGENICITY

(CONT.)

SCE in Murotions Mur. ond

CA in Mommolion in Cell CA in

Mommolion Cells Mommolion Trons- Mommolion Higher

Cells in Vilro Cells formorion Drosophila in Vivo Plonls Ollier Comments

(277) (290) (81,751 72?(158) 80- 107,202 (47'34) 302 (1 171106

189

(iiG,121) (472,108) (158) (120,173) 118' (2 1 9,224) 104,105

299,116

(283)

103S3

183,144 185,231 194 122,264

395 211i

266 63-,'78 6 7 A 7 1

217,259

268.,2;98

276,295 ( 1 !!ti) ( 1:iii) 4.3

28

Inhibition of mito- chondrial biogenesis in yeast

14, 104, 108

CA in mice lQj,

116

CA in oocytes

--

118

Enhancement of chr. breaks in virus infected cells

-__

171 Mut. in algae

217

Enhancement of EMS induced CA in barley roots

120,

173,

219,

224

Domi-

nant lethals in mice

277

Dominant lethals in rats

259

CA in grasshopper

266

Inhibition of RNA polymerase in vivo in rats

268

Stimulation of DNA synthesis

273

Decrease in repair capacity of pancreas cells

---

149 Promoting effect on BP induced transformation

299

Inhibition of DNA synthesis in rats

298

SCE, pos. in human lymphocytes; neg. in

V-79 cells

67

Enhances chain initiation of RNA when overall RNA synthesis is inhibited

63

Mispairing of poly- nucleotides in vitro

292

Inhibition of human DNA polymerase

284

Inhibition of RNA synthesis in Physarum polycephalurn (slime mold)

276,

295 Stimulation of

RNA synthesis in CHO cells chick myoblasts in mice

45

Abnormal growth in gl',

283 Abnormal sperm

47' Micronucleus

15.5.

SCE in hamster cells

(16)

TABLE

3.

~ ~ ~~

Infidelily D N A D N A

o f D N A D N A D N A Mulalions Mutations Eukaryolic Damage in Repair in

Synfhesis Damage in Repair in i n S. in M i c r e Mammalian Mammalian

Metal in Vitro Prokaryotes Prokaryoles typhimurium E coli organisms Cells Cells

CrKhromium CrCL 26- Cr(II1) 21.. CrC1,

32-

(20,791 (1 53,242 ) C r ( N 0 J 3 C r 2 0 3 CrK(S0,)- 12H20 Cr(OH)SO, NazS04 Cr1(S0& Cr2(S04)3 K2S04 Cr(CH3C00)3 Cr(II1) glycine Cr-serum (NH,)CrO, (NH,),Cr20, CaCrO, C1,Cr02 CrO, PbCrO, PbCrO,.PbO chrome orange PbCrO,. PbMoO, PbCrOn-PbS04 chrome yellow K1CrO4 KICrlO, (71,153) (71) 20-

153

188(206)' (15) (1 5 4 ) 2 1 ~ (215)2 (206)' (206)l (206)

'

396

(17)

METAL-INDUCED MUTAGENICITY

(CONT.)

SCE in Mutations M u t . and

Mammalian Cells Mammalian Trans- Mammalian Higher

Cells in Vilro Cells formation Drosophila in Vivo Plants

15L25-

(25,301 15-,2? (20.26) (31,37) (149) (30,37) (150,206) (206,227) (239,291) 291,278 155 (20,30) (30)171' (38) 183,184 -32' 185(217)

206

(30127- (30,371 (206) (206) (206,158) (155) (206) (206) 20-,37- (30.37) (36,175) 2 4 233? (75,26) (206) (158) 27- 27-

206

206 206 --_ 181 (36) 206 206 206 ___ 80 149' 15-926- (38)' 78,(170) 26 1 Other Comments

-_

154,

188,

206'

Inhibition of DNA synthesis

296

Stimulation of RNA synthesis in rats in vivo

215'

Protein- DNA

crosslinking in nuclei

215'

Protein-DNA

crosslinking in human cells

12

Cr-nitrate from Merck was negative but from riedel De Haen positive

44'

Contaminated with Cr(V1)

45

Abnormal growth in muscle fibers

29'

DNA breaks (296) 281 Modification of U . V . spectra of DNA in BHK cells

gfi-.

18

Inhibition of mito- chondrial biogenesis in yeast 281

--_

168 Review

--_

170 Mut. in 'r4 bacteriophage

--

17' Pos. only in fluctuation test

22'

29' DNA breaks

44'

Pos. when dissolv 0,5

N NaOH

24

188

206' Inhibition of DNA synthesis

28

58

Micronucleus

12

Spot test in mice 215' Prot. -DNA cross

linking in mouse nuclei 215' Prot.-DNA cross

linking in human cells

261

Binding to nucleic acids

--_ 149 Promoting effect on BP induced transformation

--_ 180 DNA cross links in rat liver and kidney _- 13 C.A. in rat bone

marrow cells

(18)

TABLE

3.

I n fidelity D N A D N A

of D N A D N A D N A Mututiom Mutations Eukuryotic Damage in Repair in

Synthesis Dumuge in Repair in in S . in Micro- Mammalion Mammalian

Melal in Vilro Prokaryotes Prokaryotes typhimurium E. coli orgunisms Cells Cells

Cr/Chromium ZnCrO, ZnCrO,. Zn(OH), 44-722- 206 Cro(C0)6 (44) Cr(H2O)sCl, (190) K,(Cr(CN)e.) (190) (Cr(NH,)4H20CI)C12 (190) (Cr(NH,)40x)N03* R O (190) (Cr(NH3),Cl1)CI (190) (Cr(en),)Cl, -3H20

1%

( 190) (Cr(pn),)CI3*3H,O

1%

( 190) cis-(Cr(bipy),Ox)I *4H10

1%

19Q cis-(Cr(bipy),Cl,)CI*2H2O

L9n

19q ~is-(Cr(phen)~Cl,)C1*2.5H,O

19n

1%

(Cr(urea),)C1,*3H20 190 190 (Cr(NH,),CI)CL (i90) (Cr(NHJ5H2O)CI3 (190) tran~-(Cr(en),(sCN)~)SCN 19Q ( 190) (Cr(en),) (SCN),

190

(190) (Cr(enMC1 (237) (CrOx(NH,), C1 (237) cis-Cr(pyr),F2)Br (237) zink yellow K,(Cr(Ox),)* 3H20 ( 190) ci~-(Cr(en)~CI,)Cl* HzO (190) coso4

cos

amorph. CoS COMOO4 CO(OH), Co(CH,COO)2 (Co(NHJs)CI, Co-serum (Co(Pn),)Cl,

+

(Co(En),)I, - (Co(En),)I, D-cis(Co(En),(NO,),)Br ~-cis(Co(En)~(NO,),)Br Other Co(II1) hexaco-

ordinate complexes 232 (237) 232 232 232 232

504'

(304) Cu/Copper CUCl cu 2 s

398

(19)

METAL-INDUCED MUTAGENICITY

(CONT.)

--

SCE in Mulalions Mul. and

CA in Mammalian in Cell C A in

Cells in Vitro Cells formation Drosophila in Vivo Planrs Ot,ker Comments

Ox = oxalate en = ethylenediamine pyr = pyridine bipy = bipyridine phen = 1.10-phenanthroline pn = propylenediamine

42

Enhancement of RNA 45 Abnormal growth in Pf-(217) 67-(292) initiation

--_

51 (296) chick myoblasts 74.37- (1 70)

51

Inhibition of spon- 183,185 taneous mutation in 184,232 b. subtilis

24-

-- 17Q Mut. in

T4

bacteriophage

220

Antimutagenic action on TA 98 and TA 1538

292

Inhibition of human DNA polymerase 4.6

296

Stimulation of RNA

synthesis in rats in vivo 204' Complexes of Co(II1) show behavior identical to similar complexes of Cr(II1) and Rh(lI1) Pn = Propylenediamine En = Ethylenediamine

62

Enhancement of initiation of RNA synthesis

3 99

(20)

TABLE

3.

Infidelity D N A D N A

o f D N A D N A D N A Mufations Mufations Eukaryofir Damage in Repair in

Synthesis Damage in Repair in in S. in Micro- Mammalian Mammalian

Mefal in Vitro Prokaryotes Prokaryotes typhimurium E. coli organisms Cells Cells

c u s o , Cu(CH3COO)i Cu-bleomycin Cu-glycine Er/Erbium Er(NO,), Eu/Europium EuCI, Au/Gold HAuCL Ir/Iridium HJrCI, Fe/Iron FeCL Fe(NO3I1 FeSOI K4Fe(CNs FeCI, Fe(NO,), Fe2(SO& Fe103 113' 177

(21)

METAL-INDUCED MUTAGENICITY

(CONT.)

_-

SCE in Mutations M u l . and

CA in Mamma/ian in Ce// C A i n

Cells in Vitro Cells formalion Drosophila in Vivo Planls Other Commenls

80- 72 80- 302 67-,(296)

111

Cu" is co-mutagen 183,184

59

Mut. in micrococcus 185,233 aureus with creatine (57) -_ 161 - Inhibition of B. sub- (59)294 tilis transformation 292,161

193

Inhibition of DNA synthesis

287

Enhancement of C.A.

287

induced by isoniazid in CHO cells

292

Inhibition of human DNA polymerase

294

Enhancement of C.A. induced by ascorbate in CHO cells 296 Stimulation of RNA

synthesis in rats in vivo

183,184

2!%!

282 Enhancement of C.A.

induced by isoniazid in CHO cells

294 Enhancement of C.A.

(I:j!j) induced by ascorbate in

CHO cells

y-rays in mice seed

155

294(155)

202:

Only co-mut. with

(22)

TABLE

3.

of D N A D N A D N A Mutations Mutations Eukaryotic Damage in Repair in

Synthesis Damage in Repair in in S. in Micro- Mammalian Mammalian

Metal in Vitro Prokaryofe Prokaryotes typhimurium E. coli organisms Cells Cells

Fe/lron K3Fe(CN6 Fe dextran Fe-edta Fe-dimethyldithiocarbamate La/Lanthanum LaCI, La(NO4, Pb/Lead Pb powder Pb” PbC12 PbO PbSO, PbO2 Pb,O4 Pb(CH3COO)z Li/Lithium Li? LiCI LiNO, (241) (71,79) (71,791 (17) (17)

402

(23)

METAL-INDUCED MUTAGENICITY

(CONT.)

---

SCE In Mulalions M U ~ . and

CA in Mammalian in Cell CA in

Cells in Vitro Cells formalion Drosophila in Vivo Plants Olhm Commcnls

183,184

60-

(97) (84,94) (66,101) (189) 98-(253) 96-(117) (298)' 208,303 (265)286 100 Mut. in algae 6i-Enhancement of RNA synthesis initiation 78 Inhibition of mito- chondrial biogenesis in yeast

42'.

282

Abnormal sperm assay

412.

91

Micronucleus

99

Dominant lethal

108 C.A. in bone marrow in mice

102 Early fetal death in mice 17Q Mut. in 7'4 bacteriophage

263

C.A. in lymphocytes from monkeys

275

Induction of RNA synthesis in mouse kidney

292

Inhibition of human DNA polymerase

298

Pos. in human lymphocytes. Neg. in V-79 cells 164 Review

302 Only Co-mut. with y-rays

-__

fiz

Enhancement of RNA

(217)297 (67) synthesis initiation 183,184

$3

Mispairing of polynu- cleotides 219 Dominant lethal in (63,671 mice 17-(183) ?,@ Mut. in algae 125 Mut. T4 bacteriophage

403

(24)

TABLE

3.

In fidelity DNA DNA

o f D N A DNA DNA Mutations Mutations Eukaryoric Damage in Repair in Synthesis Damage in Repair in in S . in Micro- Mammalian Mammalian Metal in Vifro Prokaryotes Prokaryores typhirnurium E. coli organisms Cells Cells

MnSO, 79- KMn04 (79)242? Mn(CH,COO), Mn-glycine Hg(CH,COO)z CH3HgCH, CH,HgCI CH,HgOH CH,Hg dicyandiamide C,H,HgCI C2H,-Hg-cysteine bis(C,Hs-Hg)HPO, C,H,HgBr C,H,HgCI C6HX3HgBr CH30CH,HgCl CH,0C,H5HgCI C6H5HgC1 ( 182) basic C6H5HgN0, C6H,HgOH CHjHgOCOCH, C6H,HgOCOCH,

71 -,IS-

(182) C6H,Hg dinaphtylmethane (182) disulfonate Mercaptomerin Mo/Molybdenum MoS, MoCl, H,MoO., MOO, CoMoO, K,MoO, Polymol ybdate (NH,)~MO,OM 19-

404

19-

(25)

METAL-INDUCED MUTAGENICITY

(CONT.)

SCE in Mutations Mur. and

CA m Mummalion in Cell C A in

Mammalian Cells Mummalion Trans- Mammalian Higher

Cells in Vitro Cells formation Drosophila in Vivo Plants Oih,?r Comments

220 22Q 216

27A214)

59

Mut. in Micrococcus aureus 1?,(77) (219) (217,302) 67-,1194

282

Enhancement of C.A. 80- 2QQn,;/96 induced by isoniazid in

63

- CHO cells (57)183

294

Enhancement of C.A. 185,233 induced by ascorbate in CHO cells

125

296

Stimulation of RNA synthesis in rats in vivo (!9) (220)' (220)'229 157

225

232 173?

231

(47,283) 221,221 114,262 114'

226

(220)' (59)2$!6? 228? ,268 292( 155) (155) 222,222

2.1

3 2:28 112.8

___

114' C.A. in mice 173 Dominant lethals

59

Mut. in Micrococcus aureus

228

Abnormal mitosis in Hela cells

22Q

Effects on mouse ovary

229

Early embryo death in mice

222,

223

Colchicine mitosis in human lymphocytes

212

Aneuploid cells

198

42

Sperm abnormality and micronucleus in mice

268

Stimulation of DNA synthesis

283

Sperm abnormality in mice

292

Inhibition of human DNA polymerase 296 Stimulation of RNA

synthesis in rats, in vivo

155

pip = piperdine

___

191 DNA synthesis inhibition

(26)

TABLE

3.

In fidelity DNA DNA

o f D N A DNA DNA Mutations Mufalions Eukaryofic Damage in Repair in Synthesis Damage in Repair in in S . in Micro- Mammalian Mammalian Metal in Vitro Prokaryotes Prokaryofes typhimurium E. coli organisms Cells Cells

Nd/Neodymium NdN03 Nb/Niobium NbC1, OdOsrnium

oso,

Pd/Palladium cis-(PdCI,(N,H,)) cis-(Pd(Q3 (pip13 PdCI2 Ni/Nickel Ni powder NiCo3 NiC1, NiO Ni,O, Ni,Se, (NiS) unspec. Ni,Sl NiS Amorphous NiS NiS0, (191)' 191' K1Ni(CN4 Ni(CH,COO), Ni(CO), Ni-serum Ni-propylenebis Ni-dimethyldithiocarbamate dithiocarbamate

254'

(27)

METAL-INDUCED MUTAGENICITY

(CONT.)

--

SCE in Mulalions M U ~ . and

CA m Mammalran in Cell CA m

Mammalian Higher

Cells in Vitro Cells formation Drosophila in Vivo Plants Other Comments

Mammalian Cdls Mammalian Trans-

-- 183 184 --_ 151

214

236 12-,163

(75)

236,298'

15_5(298)'

3'0.1

(3194)

9

DNA breaks and DNA- protein crasslinks __- 196 Hostmediated assay

28

Inhibition of mito- chondrial biogenesis in yeast

6

Abnormal mitosis in muscle cells in rat embryo

1'

2

240 1'

DNA breaks __- 170 Mutation in T4 bacteriophage

42

Abnormal growth in chick myoblasts

242'

25Q'

After reduction with LiAIH,

254

Strand breaks

288

Inhibition of RNA polymerase in hepatic nuclei; in vivo rats

292

Inhibition of human DNA polymerase 298 Pos. in human lymphocytes neg. in V-79 cells

149

Promoting effect on BP induced transformation thesis in mammalian cells

__

151

Mn dust reduced the transferring activity -_

304 DNA repair syn-

(28)

TABLE

3.

of D N A D N A D N A Mufalions Mutafions Eukuryolic Damage in Repair in

Synthesis Damage in Repair in i n S. in Micro- Mammalian Mammalian

Metal in V i m Prokaryofes Prokaryofes typhimurium E. coli organisms Cells Cells

NH~(P~(NHJ)CL) PtCI(NH3)j'

+

PtCLNH3' (Pt(NH3)jCl)CI K(PtNH3)CL) Pt(NH&CIz C~S-(P~(NH,)~CI. trans-(Pt(NH3),CI4 cis-(Pt(NH3),(H,o),)(N0,), trans(Pt(NH,),(H,O)d (NO,), MePtCls" cis(Pt(en)ClJ (Pt(en)3CI4 (Pt(en)(H,O)~)(NO3)2 (Pt(en) (NHA)CI, (Pt(dien)CI)Cl Pt(NH,),-oxalate Pt( NH3),-malonate (Pt(CHMpn)CL (Pt(CH,),(pn)) malonate cis-Pt(CsHI.(NH2),CI~ trans ( - ) ddcp trans (+) ddcp cis-sulfato - 1,2 diamine cyclohexane PtII SHP trans (-) SHP trans ( + ) SHP cis-Pt (py),CL ~is(PtCl,(pip)~)H20 cis(PtCI),(N,H,),)Cl, cis(Pt(C1,) (me-pipz),) Pt(CsHm(NHAWO3)* ddcp 71 (71) 237 243

131,134

128 246

245

126,122 234,237 232(246) 245? 122(234) 237 235 235 126 235 (126) 138,138' 138 138 138 (138)' K/potassium KCI KCN KOCN KOH (76,241) (71)

408

138

155

138 138 (138) 138 234

234

234 234 234

138

135

191

'

191'

(191)' (177)

(29)

METAL-INDUCED MUTAGENICITY

(CONT.)

SCE in Mutations Mut. and

C A in Mammalian in Cell C A in

Mummalian Cells Mammahan Trans- Mommalian Higher

Cells In Vitro Cells formarion Drosophila in Vivo Plants Other Comments

(136,132)

133,129

138,132

138,125.

_--

136,72

IS-

(3) 183

138’

DNA synthesis inhibition linking

260 DNA- DNA cross-

en -ethylenediamine pn - propylenedi- amine py -pyridine pip - piperdine me-pipz- methylpipera-

191

DNA synthesis dien H,N-CH,-CH,-NH- zine inhibition CHZ-CHZ-NH, (297) (67) 62 Enhancement of RNA 184 initiation

409

(30)

TABLE

3.

Injdelity D N A D N A

of D N A D N A D N A Mutations Mufalions Eukoryotic Damage in Repair in

Synthesis Damage in Repair in in S . in Micro- Mammalian Mammalian

Metal in Vitro Prokoryotes Prokaryoles typhirnurium E. coli organisms CeNs Cells

~ -~ K/potassium KH,PO, (76) KzHPOa (76) K(CH,COO) (76) K-sorbate KNO, (71) KHSO, Rh/Rhodium Rh(NOJ RhClz RhCI, (Rh(NH&Cl)CL (R~(NHJ),CL)CI RhCL(HzO), Rh(CH,CN),CIJ (Rh(en),)Cl, cis(Rh(en),C1,)Cl trans( Rh(en),Cl,)Cl ( R h ( ~ n ) ~ ) c L cis(Rh(trien)CI,)Cl Rh(pyr),CL mer(Rh(~yr),(SCN)d f a c ( R h ( ~ ~ M s c N ) J trans(Rh(pyr).,Br,)Br trans(Rh(pyr),Cl,)CI cis( Rh(bipy),Cl,)CI (Rh(bi~y)~)Cl, (Rh(phen)XI, cis(Rh(phen),Cl,)Cl trans(Rh(3-pic).,CI2)Cl Ligands alone: K,(Rh(ox)3) trien 3-pic en PYr bipy CHXN phen Pn Rb/Rubidium RbCl Rb(NO4 RbC1z Ru/Ruthenium RuCL RuCL(DMSO), (Ru(NWsC1)CL (Ru(NHJ,Ado)Br, (Ru(NH&)CI *3HzO -71 (79) -71 (237,43) 43-23? 43-23? 43-232 43-(237) 4 3 2 3 2 (43,237) (43) 43-23? (237) (43,237) (43) (43,237) 4 3 2 3 2 43-,237 43-232 (43) (43,237) 43-23? 43-23? 43- (43)? (43) (43) 43-? (43) (43) (43) (71) (76) (79) 71 71 (237,43) 43-23? 43-23? 4 3 2 3 2 (43,237) 4 3 2 3 2 (43,237) (43) 43-23? (237) (43,237) (43) (43,237) 43.232 4 3 2 3 2 43-232 (43) (43,237) 4 3 2 3 7 43-232

410

(31)

METAL-INDUCED MUTAGENICITY

(CONT.)

SCE in Mutotions Mut. and

Mummulion Cells Mammolian Trans- Mammolian Higher

Cells m Vitro Cells jormation Drosophila in Viva Plunfs Other Commenls

en - ethylenediamine pn - propylenediamine trien - diethylenetriamine pyr

-

pyridine bipy - bipyridine phen

-

phenanthroline 3-pic

-

3-Picoline ox -oxalate 184 39 There is Q progressive increase in revertants from 1 to 9

41

1

(32)

TABLE

3.

In fidelity DNA DNA

of DNA DNA DNA Mutations Mutations Eukaryolic Damage in Repair in

Synthesis Damage in Repair in in S. in Micro- Mammalian Mammalian

Metal in V i m Prokaryotes Prokatyoter typhimurium E. coli organisms Cells Cells

Ru/Ruthenium (Ru(NH,),Gua)CI, (Ru(NH3)4l-rneCyt) (BF& (Ru(NH,)~I~o)CI, (Ru(NH,),(l ,3-Me1Xan))C1, (Ru(NHJ~~GuO)CL (M NH ,) ~H Y P) C L Se/Selenium Na,Se Se Se(IV) SeO, H,SeO, K,SeO, Na,SeO, Se(V1) H,SeO, K,SeO, NaSeO, Selenocystine Selenocystamine Selenomethionine Si/Silicon Si,N, SiO, N a S i F N a S i 0

,

Ag/SiIver AgCl AgN0,2 AgiSO, Na/Sodium NaN, NaCl 19- 39- 39- 39- 39- 39- 139 (205) (79) 145(205)