Diverse chemical carcinogens fail to induce G 1 arrest in MCF-7 cells

Abstract

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.