Screening for non-genotoxic carcinogens based on induction of AID

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The molecular mechanisms underlying the carcinogenic activity of non-genotoxic (Ames mutagenicity test-negative) carcinogens are not fully understood. Given recent findings that ectopic expression of activation-induced cytidine deaminase (AID) in somatic cells play a critical role in carcinogenesis, we investigated whether several of the established non-genotoxic carcinogens induce AID expression. We examined the AID promoter activity of the established non-genotoxic carcinogens; Results showed that o-phenyl phenol and cadmium chloride (Cd) increased the promoter activity of AID in a dose-dependent manner, and actually induced AID mRNA expression. Our study demonstrated several non-genotoxic carcinogens including Cd have the potential to induce the AID gene, suggesting that this may represent a novel molecular mechanism of carcinogenesis of non-genotoxic carcinogens.