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I V
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V
D I SC U S SI O N
2
5
F I
G
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S
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3
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4
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5
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m i
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2
6
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7
N
am
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4
8
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9
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M
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6
1
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12
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M
R
sp
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t
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1
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M
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6
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14
N
M
R
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1 5
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R
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of
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1
6
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sp
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1 7
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1
8
N
M
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s
p
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4 5
19
N
M
R
s
p
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nt
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ne
4
6
2 0
N
M
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sp
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3
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2
1
N
M
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sp
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2 2
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2 3
M
a s s sp
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l
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2
4
M
a s s sp
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l
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c o nt
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2
5
M
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2
2
6
M
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m
of 1
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5 3
2 7
M
as s s
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2
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M
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it
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y
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5
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9
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l
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3
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1.
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-a c et
am i d
o-8
-h
y
dr o x
y
f l
u o r a nt
h
e n e6
0
3
4
M
a s s sp
e ct
r um
of
1
-a c et
am i d
o-8
-h
y
d
r o xy f l
u o r a nt
h
e n e(
c o nt
d
)
6
1
3
5
M
a s ss
p
e ct
r um
of
3
-n
i
t
r o-8
-h y d
r o x
y
f lu o r a n
t
h
e n e6 2
3 6
M
a s s sp
e ct
r um
of
3
-nit
r o-8
-h
y
d
r o xy
f lu o r a n
t
h
e n e(
c o nt
d
)
6 3
3 7
M
a s s sp
e ctr u
m
of 3
-n
it
r o-2
-h y d
r o xy
f lu
o r a nt
h
e n e6 4
3
8
M
a s
s sp
e ct
r um
of 3
-nit
r o-2
-h
y
dr o x
y fl
u o r a nt
h
e n e(
c o nt
d
)
6 5
3
9
M
a s s sp
e ct
r um
of 3
-a c et
am i d
o-8
-h y d
r o xy
f lu o r a n
t
h
e n e6 6
4 0
M
a s s sp
e ct
r um
of
3
-a c et
am i d
o-8
-h
y
d
r o xy
f l
u o r a nt
h
e n e(
c o ntd
)
6 7
4 1
M
a s ss
p
e
ct
r um
of 3
-ac
et
am i d
o
-2
-h y d
r o xy f l
u o r a nt
h
e ne
6
8
4 2
M
a s s sp
e ct
r um
of
3
- a c et
am i do
-2
-h
y
d
r o xy
f l
u o r a nt
h
e n e(
c o nt
d
)
6 9
4
3
A m
e sm
uta
g
e ni
ci
t
y
a s s ay
r e s ul
t
s7 0
I
I N T R O D U C T I O N
N it
r at
ed p
ol y
cy
cl i
c a r om
at
i
ch
y
d
r o c a rb
o n s(
N i
t
r o-P
A H
s)
o r ni
t
r o a r e n e s a r e ac
l
a ss
of f
us
ed
ri
ng
a r om
at
i
ch y d
r o c a rb
o n s,s
u
b
st
i
t
ut
ed w i
t
h
o n
e o rm
o
r e ni
t
ro
g
r o up
sI
n co
m p l
et
e c om b
u st
i
o np
r o c e s s e s a r et
h
ep
r ed
om i
n e nt
s o u r c e of m
o st
of
th
e ni
t
ro
a r e n e sd
et
e ct
ed
in
t
h
e e n vi
r o nm
e nt
(
Z
i
el i
n sk
a at
al
,1 9 8 6
)
N i
t
r o a r e n e sd i
sp
l
ay
ab
r o ad
s
p
ec t
r um
of m
ut
ag
e ni
c,
g
e n ot
ox
i
c a nd
c a r ci
n og
e ni
cp
r op
e rt
i
e sS
om
em
em
b
e r s of
t
h i
sg
r o up
a r ed i
r e ct
a ct
i
ng m
ut
ag
e n sth
at
d
ep
e nd
up
o n r ed
u ct
i
o n of
t
h
e ni
t
r of
u n ct
i
o nb y
b
a ct
e ri
al
ni
t
r o r ed
u ct
a s e s,w h i l
e ot
h
e r s e xh i b i
t
o nl
y
l
ow
l
e v el
s of p
ot
e n cy
, o r r eq
ui
r em
et
ab
ol i
c a ct
i
v at
i
o nO f
t
h i
sc
l
a s
so
f
c om p
o u nd
s
, ni
t
ro
p
y
r e n es a
nd
nit
ro
f l
u or
an
th
e ne s
ar
e ub i q
ui
t
o u
se n v
i
r o nm
e nt
al
c o nt
am i
n a nt
s, a nd
a r e of p
a rt
i
c ul
a r c o n c e r nb
e c a u s e of
th
em
ut
ag
e ni
c a nd
c a r c
in
og
en
i
cp
r op
e rt
i
e st
h
a
t t
h
ey
d i
sp l
ay
(
B
al l
et a
l
,1 9 8 6 ;
B
a u e ra
nd H
o
w
a
rd
,1 9 9 1 ;
E l
-B
ay
o um y
et
al
,1 9 8 8 ;
S
ug
i m
u r a a nd T
ak
ay
am
a,1 9 8 3
)
St
ud i
e sh
a v e sh
ow
nt
h
at
ch
em i
c al
sp
e ci
e sth
at
r e a ct
w i
th D N A
t o
p
r od
u c
et
um
o r sa
r e n ot
n e c e s s a ri l
y t
h
ep
a r e nt
c om p
o
u nd
s
,b
ut c
o ul d
al
s ob
e
m
et
ab
ol i
t
e s of
t
h
ep
a r en
t
c o
m p
o u nd
s,th
at
a r ef
o rm
ed
a si
nt
e rm
ed i
at
e s of
ch
em i
ca
l
r e a ct
i
o n st
h
at t
h
e c om p
o u nd
su n
d
e rg
oF
o r e x am
p
l
e, s om
em
et
ab
ol i
t
e s of
ni
t
r op
y
r e n e,th
e nit
r op y
r e n ol
s a nd
a c e
t
am i d
o
p y
r e n ols
h
a v et
e st
ed
p
o si
t
i
v ei
nm
u
t
ag
e ni
c
it
y
a s sa
y
s
B
y
a n al
o
g y
w i
t
h
n
i
t
r op
y
r e n e,it
w
a sh
y
p
ot
h
e si
z ed
th
at
nit
r of l
u o r a nt
h
e n em
et
ab
ol i
t
e s- n
i
t
r of l
u o r a nt
h
e n ol
sa
nd
a
c et
a
m i d
of l
u o ra
nth
e no
l
s
w
o ul d
al
s ob
e a ct
i
ve
T h i
sw
a sth
e r e a s o nf
o rt
h
e n e c e s si
t
y
t
o
ob
t
ai
nt
h
em i
n s uf f
i ci
e nt
q
u a nt
it
i
e si
n o rd
e rt
ob
e ab l
et
ow
o rk w it
h
t
h
em
T
h
ep
a rt
i
c ul
a r ob
j
e ct
i
v e s of
t
h i
s r e s e a r ch w
e r et
o ch
em i
c al l
y
s
y
nt
h
e si
z eb y
a
ne
f f
i ci
e nt
m
eth
od
,t
h
em
et
ab
ol i
t
e s(
p
ri
n ci
p
al
l
y
,t
h
e o xi d
at
i
o np
r od
u ct
s)
of
1
-ni
t
r op y
r e n e,3
-ni
t
r of l
u o r a nt
h
e n e a nd
of
t
h
e o xi d i
z ed
d
e ri
v at
i
v e s of
1
- am i
n op y
r e n e a nd
3
-a
m i
n of l
u o r a nth
e n eT h
e st
r u ct
u r e s of
t
h
em
et
ab
ol i
t
e s sy
nt
h
e si
z ed
w
e r et
h
e nb
ech
a r
act
e
ri
ze
d
us
i
ng
a n al y
t
i
ca
l
ch
em i
st
ry
t
e ch
ni q
u e sT h
em
et
ab
o
l i
t
e sw
e r et
h
en
b
e
I I
L I T E R
A
T
U
R E R E
V
I E
W
I I
A
N i
t
r oP
A H
si
nt
h
e e n vi
r o nm
e nt
N i
t
r at
ed
p
ol
y
cy
cl i
c a r om
at
i
cl
iy
d
r o c a rb
o n s a r e e n vi
r o nm
e nt
al
c o nt
am in
a nt
sw i d
el
y
p
r e s e nt
i
n ai
rb
o r n ep
a rt
i
c ul
at
em
at t
e r, a sd
et
e ct
ed f
r om
e n vi
r o nm
e nt
al
s o u r c e si
n cl
u
di
ng
d i
e s el
a nd
g
a s ol i
n e e ng i
n e em
i
s si
o n s,
c
i
g
a r et t
e sm
ok
e c o nd
e n s at
e s,f l
y
a sh
p
a rt
i
cl
e s,
u
s ed m
ot
o r oi l
, a nd
em i
s si
o n s o ri g i
na
t
i
ng f
ro
m i
n ci
n e r at
o r s, r e si d
e nt
i
al h
om
eh
e at
e r s a nd w
o od b
u r ni
ng
st
o v e s(
R
o s e nk
r a n z a nd
M
e rm
el
st
ei
n,
19 8 5
)
1
-N i
t
r op
y
r e n eh
a sb
e e nd
et
e ct
ed i
n ai
rb
o r n ep
a rt
i
c ul
at
e o rg
a ni
cm
at t
e r(
P
i
t t
s et
a
l
,1
9 7
8
)
,d i
e s el
e xh
a u st
p
a rt
i
c ul
a
t
em
at t
e r(
S
ch
u et
zl
e,1 9 8 3
)
,c
o al f l
y
a sh
(
M
um f
o rd
a nd
L
ew
t
a s,1 9 8 2
)
,w
o od
st
o v e em i
s s
i
o n s(
G i b
s o n,
1 9 8 2
)
, s e r vi
c e st
at
i
o n ef fl
u e nt
(
M
a n ab
e et
a
l
,1 9 8 4
)
,p h
ot
o c op i
e rt
o n e r s(
R
o s e nk
r a n z et
al
.,1 9 8 0
)
a nd i
nJ
ap
a n e s eg
ri l l
ed
ch i
ck
en
(
K i
n
ou
ch i
et
al
,1 9 8 6
)
2
-N i
t
r of l
u o r a nt
h
e n eh
a sb
e e nd
et
e ct
ed i
n e xt
r a ct
sf
r om
am b i
e n
t
ai
rp
a rt
i
c ul
at
em
at
t
e rf
r om
u rb
a n a nd
r u r al
a r e a s(
N i
el
s e n et
al
,1 9 8 4 ; P
i
t t
s et
al
,1 9 8 5
)
3
-N i
t
r ofl
u
o r a nt
h
e n eh
a sb
e e nd
et
e ct
ed m
ai
nl
y
i
nd i
e s el
em i
s si
o ns
(
P
ap
ut
a-P
e c
k
e
t
al
,1 9 8 3 ;
S
ch
u et
zl
e,1 9 8 3
)
I I
B
F
o rm
at
i
on
of N i
t
r o-P
A H
sN i
t r
o-P A H
s
w
e r ef
o rm
ed b
y t
h
e ni
t
r at
i
o
n of P A H
sp
r e s e nt
i
n c om b
u
st
i
o ng
a s e s a nd
o np
a rt
i
c ul
at
em
at t
e r ei
t
h
e rd
u ri
ng
c om b
u st
i
o n o rw h i
l
e ci
r c ul
at
i
ng
i
n am b i
e nt
ai
r(
N i
el
s e n et
al
,1 9 8 4 ; Z
i
el i
n sk
a et
al
,1 9 8 6
)
1
-N i
t
r op y
r e n e, ad i
r e ct
b
y
-p
r od
u ct
of i
n c om p l
et
e c om b
u sti
on
p
r o c e s s e s,
w
a si d
e nt
i f i
ed
a st
h
e si
ng
l
em
o st
ab
u nd
a nt
ni
t
r o-P A
H i
nd i
e s el
e ng i
n e e xh
a u st
(
P
ap
ut
a-P
e ck
e
t
a
l
,1 9
83
)
I t
w
as
f
o rm
ed
sy
nt
h
et
i
c al l y
o nf
il
t
e r sb y
t
h
e r e a ct
i
o n of p y
r e n ew i
t
h g
as e
o u sN
2
O
5
(
P
i
t t
s
et
al
,1 9 8 5
)
3
-
N i
t
r of l
u o r a nt
h
e n e,
a
l
s
oi d
e nt
i f
i ed
a s a c om b
u st
i
on
b
y
-p
r od
u ct
i
nd i
e s el
e ng
i
n e e xh
a u st
,w
a s r e ad i l
y p
r od
u c ed b
y
t
h
ed i
r e ct
nit
r ati
o n of
th
efl
u o r a nt
h
e n em
ol
e cu
l
eb
y
N
r e
p
o rt
ed
t
h
at t
h
e r e a ct
i
o n of
f l
u o r a nt
h
e n ew
i
t
h
N
2
O
5
o nf
il
t
e r sf
o rm
ed
t
h
e1
-,3
-,
7
- a n
d
8
-i
s
om
e rs
of
nit
r of l
u o r a nt
h
e n e(
Sw
e et
m
a
n et
al
,
1 9 8 6
)
2
-N i
t
r of l
u o r a nth
e n e,
f
o rm
ed
p
r ed
om i
n a nt
l
y
i
n am b i
e nt
ai
r,w
a sf
o rm
ed b
y
t
h
er e a c
t
i
o n of
v ol
at
i l
e o rg
a ni
cf l
u o r a nt
h
e n e sw i
t
h N
2
O
5
af
t
e rf
r e e r ad i
c al f
o rm
at
i
o n at t
h
e
C
-3 p
o si
t
i
o n(
P
i
t ts e
t
al
,1 9 8 5 ; Z
i
el i
n sk
a et
al
,1 9 8 6 ; Z
i
el
i
n sk
a et
al
,1 9 8 7
)
I I
C
S
t
r u ctu r e
A
ct
i
vi
t
y R
el
at
i
o n sh
i
p
s(
SA
R
)
T
h
eg
e n ot
ox
i
ci
t
y
of
ni
tr o
-P A
H
si
nt
h
eS
al m
o n el l
at
y p
h i
m
u ri
um
p
l
at
ei
n co
rp
o r at
i
o n as
s ay
i
sl
a rg
el
y
d
u et
ot
h
ei
nte r a c
t
i
o n of
a n a ry
l
ni
t
r e ni
um
i
o nf
o rm
ed
t
h
r o ug h
r ed
u ct
i
o n of
t
h
e ni
t
r og
r o up
P
r ot
o n at
i
o n of
th
eh
y
d
r o xy
l
am i
n ei
nt
e rm
ed i
at
er e s u
l
t
si
nt
h
el
o s s of
aw
at
e rm
ol
e c ul
ef
r om
t
h i
s c om
p
o u nd
a nd f
o
rm
at
i
on
of
t
h
en
i
tr e
n
i
um i
o n ,t
h
e ul
t
i m
at
e r e a ct
i
v e sp
e ci
e sth
at
b i
nd
sto
D N A
D
el
o c al i
z at
i
o n of
th
ep
o si
t
i
v e ch
a rg
ef
r om
t
h
e ni
t
r e ni
um i
o ni
nt
ot
h
e a r om
at
i
c ri
ng p
r od
u c e s c a rb
o ni
um i
o n s at
t
h
e o rt
h
o a nd p
a r ap
o si
t
i
o n sT
h
el i f
et
i m
e of
t
h
e ch
a rg
ed
el
e ctr o
p
h i l
ew
o ul d b
ei
n c r e a s ed
1
^^
b y
st
ab i l i
z at
i
o n of
t
h
e a r om
ati
c c a rb
o ni
um i
o n,l
e ad i
ng
t
oan
i
n c r e as
ei
n
i
t
s
c
h
a
n c es o
f
b i
nd i
ng
t
oD
N A
I
n c r e a s ed f
o rm
at
i
o n of D N A
a
d d
u ct
s
w
o ul d i
n c r e as
em
ut
ag
e ni
cp
ot
e n cy
V
a n c e a nd
L
e vi
n(
1 9 8 4
)
h
a v ed
ete r
m i
n ed
t
h
at
f
o u rf
a ct
o r sf
a v o r ni
t
r o- r ed
u
ct
i
o no
f
t
h
en
i
t
r o-P A H
sb
y
S
al m
o n el l
at y
p
h i m
u ri
um
a nd h
e n c ee
nh
a n c et
h
ef
o rm
at
i
on
of
th
ee
l
e ct
r op
h i l i
cm
et
ab
ol i
t
e st
h
at
r e a ct
w i
t
h
D
N A
T
h
e st
r u ct
u r e a ct
i
vi
t
y
r el
at
i
o n sh i p
sd
ef i
n
ed
a r e :(
1
)
P h y
si
c al d i m
e n si
o n a nd d
eg
r e eo
f
a r om
at
i
ci
t
y
(
2
)
I
s om
e ri
cp
o si
t
i
o n of
t
h
e ni
t
r og
r o up
(
3
)
C
o nf
o rm
at
i
o n of
t
h
e ni
t
r og
r o up
w i
t
h
r e sp
e ct
t
ot
h
ep
l
a n e of
t
h
e a r om
at
i
c ri
ng
s.(
4
)
A b i l i
t
y
t
o r e s o n a n c e-s
t
ab i l i
z et
h
e ul
t
i m
at
e el
e ctr o
p h i l
eA
cc
o rd i
ng
t
ot
h
e r eq
ui
r em
e nt
s s et
f
o rt
h b
y
V
a n c e a nd L
e vi
n(
1 9 8 4
)
,3
-n
i
tr o
f l
u o r a nt
h
e n ew
as
p
r
ed i
ct
ed
a nd f
o u nd
t
ob
e ah i g h l y m
ut
ag
e ni
c c om p
o
un
d I
t
h
a s
t
h
e op
t
i m
u
m l
e ng
t
h
-n
i
t
r ob
e n z o[
k
]
fl
u o r a nt
h
e n ew
a sf
o u nd
to
h
a v e r ed
u c ed m
ut
ag
e ni
cit
y
I
t
w
a s ob
s e r v ed
th
at
n
it
r e-P
A
H
sw i
th
ni
tr e
g
r o up
s st
e ri
c al l
y
f
o r c ed
o ut
-of
-p
l
a n e of
th
e a r om
at
ic r
i
ng
st
r u ct
u r ew
e r ew
e ak l
y
m
ut
ag
e ni
c o r n o nm
ut
ag
e ni
c(
V
a n c e a nd
L
e vin
,1 9 8 4
)
T
h
e c au
s ef
o rt
h
en
it
r eg
r o up
t
ob
e o ut
of
a c op
l
a n a rp
o sit
i
o nw
a st
h
el
o c at
io n
of
th
e ni
t
r e s ub
st
i
tu e n
t
b
et
w
e e nt
w
op
e ri p
o si
t
io n s o r
in
ab
ay
r eg i
o nT
h
eg
e n ot
o xi
ci
t
y
of
nit
r e-P
A H
sw
a s e nh
a n c ed
b
y
st
r u ctu r a
l f
e at
u r e sth
at
c o n
t
ri b
ut
ed
t
ot
h
e r e s o n a n c e st
ab i l i
z at
i
o n of
th
e r e a cti
v e ni
t
r e ni
um i
o n(
V
a n c e a nd
L
e vin
,1 9 8 4
)
I I
D
M
eta
b
ol is
m
of N it
r e-P
A H
sU
nd
e r a n a e r ob ic
in c u
b
at
i
o n c o nd i
t
i
o n s,b
a cte r
i
al
a nd m
am m
al i
a n e n zy
m
at
ic
s
y
st
em
s sh
ow
ed
t
h
e c ap
a ci
t
y
t
op
a rt
i
cip
ate
i
nt
h
e r ed
u cti
v em
et
ab
ol i
sm
of
nit
re
-P A H
s(
R
e s e nk
r a n z a nd
M
e rm
el
st
ein
,
1 9 8 3
)
I I
D
1 B
a ct
e ri
al
m
eta
b
ol i
sm
B io
lo
g
i
c al
a cti
v ati
o n of m
o st
ni
tr e
-P
A
H
s
is
t
h
o ug h
t
to
o c
c u rt
h
r o ug
h
t
h
ee n z
y
m
at
i
c a ct
i
o n of
nit
r o r ed
u ct
a s e e n zy
m
ep
r e s e nt
in
th
eSa
l m
o n el l
at
v
p h i m
u ri
um
s
tr a
i
n sT
h
e ni
tr o r e
d
u ct
a s e s c o n v e rt
1
-ni
tr e
p
y
r e n et
o1
-ni
tr o s e
p
y
r e n e a nd
t
h
e nt
ot
h
ec o r r e s
p
o nd i
ng
N
-h
y
d
r o xy
l
am i
n eP A H
T h
r e ep
at
h w
ay
sh
a v eb
e e n s ug g
e st
ed f
o rf
u rt
h
e rm
et
ab
ol i
sm
of
t
h
eN
-h
y
d
r e xy
l
am i
n oP
A H
i
nt
e rm
ed ia
t
e sO
n ep
at
h w
ay
in v o
l
v ed
a ci d
c a
t
al
y
z ed
d
e c om
p
o si
t
i
o n of
th
ei
nte r
m
ed
i
at
et
op
r odu c e
h
i
g
h l
y
el
e ct
r ep h
i l i
ca r
y
l
ni
tr e n
i
um i
o n sth
at
c o ul d b i
nd
t
oD
N A
(
K
a rp
in s
k
y
et
al
,1 9 8 2 ;
H
ow
a rd
et
al
,1 9 8 3
b
;
P
at t
e ne
t
al
,1 9 8 6
)
A
s e c o nd p
ath w
ay
i
n v olv e
d
e n zy
m
at
i
c r edu c
t
i
o n of
t
h
ei
nt
e rm
ed i
at
et
of
o rm
am i
n o-P A
H
sth
at
w
e r e c ap
ab le
of
u nd
e rg
oin
g
a c et
y
l
at
i
e nt
of
o rm
a c et
am i do
-P
A
H
sT
h
et
h i
rd
p
at
hw
ay
in v o
l
v ed d ir e c
t
e n zy
m
at
i
c0
-a c et
y
l
at
i
o n of
t
h
eh
y
d
r e xy
l
am i
n ei
nt
e rm
ed i
at
eb
y
th
e0
-a c et
y
lt
r a n sf
e r a s e e n zy
m
et
of
o rm N
-a c et
ox
y
P A
H
sw h i
ch w
e r ec a