‘Stealth Properties’ Contribute to the Potent Action of Polycyclic Aromatic Hydrocarbon Carcinogens

Autor: Karen H. Vousden, Anthony Dipple, Qasim A. Khan
Rok vydání: 2000
Předmět:
Zdroj: Polycyclic Aromatic Compounds. 16:89-98
ISSN: 1563-5333
1040-6638
DOI: 10.1080/10406639908020576
Popis: Dihydrodiol epoxides are carcinogenic metabolites of polycyclic aromatic hydrocarbons. The effects of two such compounds, benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide and 5-methylchrysene 1,2-dihydrodiol 3,4-epoxide, on the progress of the human mammary carcinoma cell, MCF-7, through the cell cycle was investigated. Unlike other DNA damaging agents, such as actinomycin D, these carcinogens did not arrest MCF-7 cells in the G1 phase of the cell cycle and the cells began DNA replication despite the damage in the DNA template. The dihydrodiol epoxides, like actinomycin D, induced the p53 protein that normally mediates G1 arrest through transcriptional activation of p21wafl/cipl, in these cells. However, increased cellular p21wafl/cipl levels were not found in the hydrocarbon-treated cells. Thus, these carcinogens did not trigger the major ‘guardian of the genome’ cellular defense mechanism mediated by p53. This stealth characteristic may be an important contributor to the carcinogenic action of ...
Databáze: OpenAIRE