Effect of duration of exposure to benzo(a)pyrene diol-epoxide on neoplastic transformation, mutagenesis, cytotoxicity, and total covalent binding to DNA of rodent cells.
We examined the effect of different durations of exposure (20 sec to 24 hr) to (+/-) 7-beta,8 alpha-dihydroxy-9 alpha, 10 alpha -epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE I) on the induction of transformation in C3H/10T 1/2 cells and of mutations to 6-thioguanine resistance in Chinese hamster ovary cells (CHO), as well as on BPDE I-DNA binding in these two cell lines. A 20-sec exposure of the cells to BPDE I was sufficient to induce mutations and morphological transformation in vitro. However, the transformation frequency in CH3 mouse-embryo-derived 10T 1/2 cells increased twofold and the frequency of mutations in CHO cells sixfold when the exposure time to BPDE I was increased from 20 sec to 8 h. Cytotoxicity increased under similar conditions. A large number of BPDE I-DNA adducts were formed in both cell lines within the first 15-min of exposure of the cells to this ultimate carcinogen. The total covalent binding did not increase with longer than 15-min incubation times. These results suggest that in addition to its covalent binding to DNA, BPDE I may influence other cellular mechanism(s) that are responsible for the initiation of transformation and mutagenesis.
Krolewski
B
B
Laboratory of Radiobiology, Harvard School of Public Health, Boston, Massachusetts 02115.
Little
J B
JB
Reynolds
R J
RJ
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis* / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000032:analysis*; D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes / Q000032:analysis* / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D009153:Mutagens; D009154:Mutation; D013997:Time Factors
D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; D009153:Mutagens; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA