Induction of activation-induced cytidine deaminase by a not-directly mutagenic carcinogen: a novel potential molecular mechanism.

Objective: The molecular mechanisms underlying the carcinogenic activity of not-directly mutagenic (Ames mutagenicity test-negative) carcinogens are not fully understood. Given recent findings that ectopic expression of activation-induced cytidine deaminase (AID) in somatic cells plays a critical role in carcinogenesis, we investigated whether several of the established not-directly mutagenic carcinogens induce AID expression.

Methods: We prepared cells with stable expression of luciferase reporter gene containing the promoter of AID. We then used this system to examine the AID promoter activity of the non-genotoxic carcinogen: butyl benzyl phthalate, bisphenol A, di (2-ethylhexyl) phthalate, cadmium chloride (Cd), and butylated hydroxyanisole.

Results: Results showed that Cd increased the promoter activity of AID and actually induced AID gene expression.

Conclusion: A not-directly mutagenic carcinogen, cadmium, has the potential to induce the AID gene, suggesting that this might represent a novel molecular mechanism of carcinogenesis of cadmium.