Diverse chemical carcinogens fail to induce G(1) arrest in MCF-7 cells.
The effect of three reactive potent chemical carcinogens on the passage of MCF-7 cells through the cell cycle was investigated. While these cells, which express wild-type p53, were arrested in G(1) after treatment with actinomycin D (a positive control), treatment with anti-benzo[a]pyrene dihydrodiol epoxide, N-acetoxy-N-2-fluorenylacetamide or N-methyl-N'-nitro-N-nitrosoguanidine, at doses consistent with survival of significant numbers of cells, caused the cells to accumulate in S phase, with little increase in those in G(1). This property of these three reactive potent carcinogens, of diverse chemical types, to induce evasion of G(1) arrest (the stealth property) presumably increases the likelihood of malignant change, because DNA replication continues on a damaged template. This stealth characteristic may be a major contributor to the tumorigenicity of DNA-adducting chemical carcinogens in general.
Khan
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Laboratory of Comparative Carcinogenesis and ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. khanq@ncifcrf.gov
Dipple
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D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000099:Acetoxyacetylaminofluorene / Q000633:toxicity; D000477:Alkylating Agents / Q000633:toxicity; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D015739:Nocodazole / Q000494:pharmacology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000477:Alkylating Agents; D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D003609:Dactinomycin; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000099:Acetoxyacetylaminofluorene; D015739:Nocodazole