The effects of cell cycle position on the cytotoxicity and mutagenicity of benzo(a)pyrene in cultured Chinese hamster cells.
The induction of cytotoxicity and mutation to 6-thioguanine resistance (6TGr) by S9-activated benzo(a)pyrene (B(a)P) was studied in asynchronized and synchronized Chinese hamster V79 cells. After treatment of asynchronized populations with B(a)P (0.25-2 micrograms/ml) in the presence of S9 for 3 h, the number of 6TGr cells increased. The increase was concentration-dependent up to 2 micrograms/ml, and was accompanied by a concomitant concentration-dependent decrease in cell survival. Synchronized cells were treated with B(a)P for 2 h at 2-h intervals after release from the G1/S block by hydroxyurea (HU). The cytotoxicity of 2 micrograms/ml of B(a)P was maximal at 0 h after HU release, i.e., G1/S phase, and also at 2 h after HU release, i.e., early S phase. Thereafter, it decreased with the progression of the cell cycle. Similarly, treatment with B(a)P at 0 h and 2 h after HU release resulted in the maximum incidence of 6TGr mutants, after which the incidence showed a decrease from 4-10 h after HU release. These results indicate that the cells in G1/S and early S phase are highly susceptible to cytotoxic and mutagenic damage induced by B(a)P and suggest the presence of a specific hot spot in the cell cycle for mutagenesis by the carcinogen B(a)P in cultured hamster cells.
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006918:Hydroxyurea / Q000378:metabolism; D009153:Mutagens; D009154:Mutation; D013866:Thioguanine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D009153:Mutagens; D014316:Tritium; D001564:Benzo(a)pyrene; D013866:Thioguanine; D013936:Thymidine; D006918:Hydroxyurea