Carcinogenic polycyclic aromatic hydrocarbons induce CYP1A1 in human cells via a p53-dependent mechanism.

ABSTRACT: The tumour suppressor gene TP53 is mutated in more than 50 % of human tumours, making it one of the most important cancer genes. We have investigated the role of TP53 in cytochrome P450 (CYP)-mediated metabolic activation of three polycyclic aromatic hydrocarbons (PAHs) in a panel of isogenic colorectal HCT116 cells with differing TP53 status. Cells that were TP53(+/+), TP53(+/-), TP53(-/-), TP53(R248W/+) or TP53(R248W/-) were treated with benzo[a]pyrene (BaP), dibenz[a,h]anthracene and dibenzo[a,l]pyrene, and the formation of DNA adducts was measured by (32)P-postlabelling analysis. Each PAH formed significantly higher DNA adduct levels in TP53(+/+) cells than in the other cell lines. There were also significantly lower levels of PAH metabolites in the culture media of these other cell li

SUBMITTER: Wohak LE 

PROVIDER: S-EPMC4748000 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature