Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives

Betel quid (BQ)-chewing is a popular oral habit with potential links to the occurrence of oral cancer. Many of the literature-based studies reveal tha t areca nut (AN) extract may demonstrate mutagenic and genotoxic effects, i n addition to inducing preneoplastic as well as neoplastic lesions in exper imental animals. Areca nut should, thus, be highly suspected as a human car cinogen. Toxicity studies relating to AN-contained polyphenols and tannins are not conclusive, with both carcinogenic and anti-carcinogenic effects be ing reported. The mutagenicity and genotoxicity of areca alkaloids has been detected by many short-term assays. However, their genotoxicity to oral fi broblasts and keratinocytes, the target cells of BQ, has not been identifie d. It would thus appear that AN toxicity is not completely due to its polyp henol, tannin and alkaloid content. The single agent which is responsible f or AN carcinogenicity awaits further clarification. Reactive oxygen species produced during auto-oxidation of AN polyphenols in the BQ-chewer's saliva , are crucial in the initiation and promotion of oral cancer. Nitrosation o f areca alkaloids also produces AN-specific nitrosamines, that have been de monstrated to be mutagenic, genotoxic and are capable of inducing tumors in experimental animals. Arecaidine and AN extract are further suggested to b e tumor promoters. Antioxidants such as glutathione and N-acetyl-L-cysteine can potentially prevent such AN-elicited cytotoxicity. Further studies are needed to delineate the metabolism of AN ingredient and their roles in the mufti-step chemical carcinogenesis, in order to enhance the success of the future chemoprevention of oral cancer and oral submucous fibrosis. (C) 200 1 Elsevier Science Ltd. All rights reserved.