Colorectal
neoplasia is the third most common
cancer worldwide. Environmental factors such as diet are known to be involved in the etiology of this
cancer. Several epidemiological studies have suggested that specific neo-formed mutagenic compounds related to meat consumption are an underlying factor involved in the association between diet and
colorectal cancer. Heterocyclic
amines (HCAs) and
polycyclic aromatic hydrocarbons (PAHs) are known
mutagens and possible human
carcinogens formed at the same time in meat during cooking processes. We studied the genotoxicity of the model PAH
benzo(a)pyrene (B(a)P) and HCA 2-amino-1-methyl-6-phenylimidazo[4,5-
b]pyridine (
PhIP), alone or in mixture, using the mouse intestinal cell line Apc(Min/+), mimicking the early step of colorectal
carcinogenesis, and control Apc(+/+) cells. The genotoxicity of B(a)P and
PhIP was investigated using both cell lines, through the quantification of B(a)P and
PhIP derived
DNA adducts, as well as the use of a genotoxic assay based on
histone H2AX phosphorylation quantification. Our results demonstrate that heterozygous Apc mutated cells are more effective to metabolize B(a)P. We also established in different experiments that
PhIP and B(a)P were more genotoxic on Apc (Min/+) cells compared to Apc (+/+) . Moreover when tested in mixture, we observed a combined genotoxicity of B(a)P and
PhIP on the two cell lines, with an increase of
PhIP derived
DNA adducts in the presence of B(a)P. Because of their genotoxic effects observed on heterozygous Apc mutated cells and their possible combined genotoxic effects, both B(a)P and
PhIP, taken together, could be implicated in the observed association between meat consumption and
colorectal cancer.