COMPARISON OF THE MORPHOLOGICAL TRANSFORMING ACTIVITIES OF DIBENZO[A,L]PYRENE AND BENZO[A]PYRENE IN C3H10T1 2CL8 CELLS AND CHARACTERIZATIONOF THE DIBENZO[A,L]PYRENE-DNA ADDUCTS/
S. Nesnow et al., COMPARISON OF THE MORPHOLOGICAL TRANSFORMING ACTIVITIES OF DIBENZO[A,L]PYRENE AND BENZO[A]PYRENE IN C3H10T1 2CL8 CELLS AND CHARACTERIZATIONOF THE DIBENZO[A,L]PYRENE-DNA ADDUCTS/, Carcinogenesis, 18(10), 1997, pp. 1973-1978
C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts were used to study t
he in vitro carcinogenic activities of dibenzo[a,l]pyrene (DB[a,l]P) a
nd benzo[a]pyrene (B[a]P). The morphological transforming activities o
f these rodent carcinogens were compared using replicate concentration
-response studies, In concentration ranges where both polycyclic aroma
tic hydrocarbons (PAHs) were active, DB[a,l]P proved to be four to 12
times as potent as B[a]P based on concentration, At lower concentratio
ns DB[a,l]P was active at 0.10 and 0.20 mu M, concentrations where B[a
]P was inactive, This makes DB[a,l]P the most potent non-methylated PA
H evaluated to date in C3H10T1/2 cells, DNA adducts of DB[a,l]P in C3H
10T1/2 cells were analyzed by both TLC and TLC/HPLC P-32-postlabeling
methods using mononucleotide 3'-phosphate adduct standards derived fro
m the reactions of anti-DB[a,l]P-11,12-diol-13,14-epoxide (anti-DB[a,l
]PDE) and syn-DB[a,l]P-11,12-diol-13,14-epoxide (syn-DB[a,l]PDE) with
deoxyadenosine 3'-monophosphate and deoxyguanosine 3'-monophosphate. A
ll of the DNA adducts observed in C3H10T1/2 cells treated with DB[a,l]
P were identified as being derived from the metabolism of DB[a,l]P to
its fjord region diol epoxides through DB[a,l]P-11,12-diol. The predom
inant adduct was identified as an anti-DB[a,l]PDE-deoxyadenosine adduc
t, Other major adducts were anti-DB[a,l]PDE-deoxyguanosine and syn-DB[
a,l]PDE-deoxyadenosine adducts with minor amounts of syn-DB[a,l]PDE-de
oxyguanosine adducts, These DNA adduct data are consistent with simila
r findings of DB[a,l]PDE-deoxyadenosine adducts in mouse skin studies
and human mammary cells in culture.