The effect of a potent mammary
carcinogen, anti
benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide, on the progress of
human mammary carcinoma MCF-7 cells through the cell cycle was investigated. While these cells, which express wild-type p53, were arrested in G1
after treatment with
actinomycin D (a positive control), treatment with the mammary
carcinogen did not cause G1 arrest but instead delayed the cells in the
DNA synthesis phase. In concert with the absence of a G1 arrest, it was found that though both chemical treatments led to increased levels of p53, only the p53 induced by
actinomycin D was transcriptionally active and increased the levels of the
cyclin dependent kinase inhibitor, p21(waf1/cip1). Since treatment of the cells with the mammary
carcinogen did not abrogate the G1 arrest induced by
actinomycin D, the lack of p21(waf1/cip1) and of G1 arrest, resulting from treatment with the mammary
carcinogen alone, was not due to some general inhibition of transcription or translation. An analogous difference between these two chemicals was demonstrated also in other human cell systems. The stealth-like property of the mammary
carcinogen that allows it to damage
DNA without turning on the cells' 'guardian of the genome' defense mechanism presumably increases the likelihood of malignant change because DNA replication continues on a damaged template. It is suggested that this stealth characteristic may be a major contributor to the high carcinogenic potency of this mammary
carcinogen and possibly to that of other highly potent
carcinogens.