Chemoprevention of Carcinogenesis by Organoselenium Compounds.

Abstract

The modifying effects of novel synthesized oragnoseleniums on carcinogenesis have been examined in several organs. p-Methoxybenzeneselenol (MBS), benzylselenocyanate (BSC) and 1, 4-phenylenebis(methylene)-selenocyanate (p-XSC) have been synthesized, respectively. MBS reduced benzo[a]pyrene (B[a]P)-induced forestomach tumors in female CD-1 mice and azoxymethane (AOM)-induced colon, liver and kidney neoplasms in female F344 rats. BSC has been effective on AOM-induced colon neoplasms and liver preneoplastic lesions in male F344 rats, and dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female SD rats. p-XSC reduced AOM induced colon neoplasms, 4-(methlynitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung neoplasms in female A/J mice, DMBA induced mammary neoplasms in female SD rats, and 4-nitroquinoline oxide(4-NQO)-induced tongue carcinogenesis in male F344 rats. BSC increased selenium-dependent glutathione peroxidase in the kidney, colon and small intestine. An increase in total liver cytochrome P-450 was also found in BSC-treated rats. Following AOM treatment, signyficantly less O6-methylguanine and 7-methylguanine was present in the colon DNA from rats consuming the BSC diet than in the rats fed control diets. Those results indicate that dietary BSC induces the enzymes to hydroxylate or oxidate the carcinogens and decrease DNA alkylation. p-XSC inhibited NNK-induced oxidative damage in the lung of A/J mice or F344 rats, DMBA-DNA adducts in rat mammary tissue, and induced apoptosis. These mechanisms may account for their chemopreventive activities.