Cellular response to DNA damage from a potent carcinogen involves stabilization of p53 without induction of p21(waf1/cip1)

Carcinogenesis
Q A KhanA Dipple

Abstract

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' de...Continue Reading

Citations

Oct 13, 2001·Cancer Letters·D StuartA Dipple
Jul 29, 1998·Molecular Medicine Today·M H Kubbutat, K H Vousden
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·P J MoosF A Fitzpatrick
Jul 19, 2013·BioMed Research International·Abderrahim NemmarErnesto Alfaro-Moreno
Mar 29, 2002·Environmental and Molecular Mutagenesis·Brandon D JeffyDonato F Romagnolo
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Sep 27, 2014·Life Sciences in Space Research·Ann R Kennedy
Jul 27, 2000·Carcinogenesis·Q A Khan, A Dipple
Nov 27, 1999·The Journal of Biological Chemistry·X H PeiN Hara
Jan 18, 2019·Journal of Ovarian Research·Long CuiChi Chiu Wang

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