Colorectal cancer initiation by benzo[a]pyrene and N-nitroso compounds in A/J Min/+ mice

Processed meat contains multiple substances with mutagenic properties, but there is limited knowledge about the combined effect of polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs). This study characterized the carcinogenic potential of single or combined dietary exposure to Benzo[a]pyrene (BaP, a PAH) and a mixture of six food-derived NOCs in the A/J Min/+ mouse model for human colorectal cancer. Mice were given diets containing low or high concentrations of BaP and/or NOCs for nine weeks. The concentrations were based on estimated daily intake levels in the European population. A sex-dependent increased CRC initiation was detected after combined exposure to the high doses of BaP and NOCs. No effects were seen on CRC following exposure to the low doses of BaP or NOCs individually or in combination. Targeted plasma metabolomics revealed alterations in cellular membranes, lipid and energy metabolism in mice exposed to the high doses of BaP and NOCs. An alteration of plasma metabolites was also seen in mice exposed to the low dose of BaP, but not in mice exposed to the low dose of NOCs or to the combined low doses of BaP and NOCs. The study highlights the complex interplay between dietary carcinogens.