Masayuki Tatemichi1, Harumi Hata, Toshio Nakadate. 1. Department of Hygiene and Preventive Medicine, School of Medicine, Showa University, Tokyo, 142-8555, Japan, tatemichi@tokai-u.jp.
Abstract
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.
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.
Authors: Khadiga S Abrahim; Nadia B Abdel-Gawad; Amal M Mahmoud; Mohamed M El-Gowaily; Ahmed M Emara; Mohamed M Hwaihy Journal: Toxicol Ind Health Date: 2010-09-24 Impact factor: 2.273
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