Interference with mutagenic aflatoxin B1-induced checkpoints through antagonistic action of ochratoxin A in intestinal cancer cells: a molecular explanation on potential risk of crosstalk between carcinogens

摘要: Foodborne aflatoxin B1 (AFB1) and ochratoxin A (OTA) cause genotoxic injury subsequent tumor formation. As a biomarker of oncogenic stimulation by mycotoxins, p53-triggered Mdm2 was assessed in intestinal cancer cells. AFB1 increased reporter expression dose-dependent manner. However, this strongly antagonized OTA treatment. positive transcription factor expression, p53 levels were also alone reduced OTA. With marginal cell death responses, induced p53-mediated S phase arrest cycle-regulating target genes, which completely suppressed Although enterocyte-dominant CYP3A5 counteracted AFB1-induced DNA damage, decreased or AFB1. Instead, enhanced another metabolic inactivating enzyme CYP3A4, attenuation formation AFB1-DNA adduct cycle checking responses to the mutagens. Finally, growth cells exposed mycotoxin mixture significantly exceeded expected calculated from that treated with each mycotoxin. mutagen OTA, interference checkpoints through antagonistic action may contribute survival deleterious mutations potently increasing risk carcinogenesis.