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/

Citation
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
Citations number
34
Categorie Soggetti
Oncology
Journal title
ISSN journal
01433334
Volume
18
Issue
10
Year of publication
1997
Pages
1973 - 1978
Database
ISI
SICI code
0143-3334(1997)18:10<1973:COTMTA>2.0.ZU;2-B
Abstract
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.