Remission of oral precancerous lesions of tobacco/areca nut chewers following administration of beta-carotene or vitamin A, and maintenance of the protective effect

Abstract

Designs of intervention trials are based on results from a multitude of disciplines. In this study, a comparative analysis of various chewing mixtures used by groups from different geographical locations (Guam, Peru, Taiwan, the Philippines, and India) and their link to oral cancer incidences was used to trace the ingredients responsible for oral carcinogenesis among chewers. The usefulness of applying intermediate endpoints in intervention trials was examined by comparing the response of micronucleated mucosal cells and oral leukoplakia of chewers of tobacco-containing betel quids to the twice weekly administration of beta-carotene (180 mg/week), vitamin A (100,000 IU/week or 200,000 IU/week), and beta-carotene (180 mg/week) plus vitamin A (100,000 IU/week). A reduced frequency of micronucleated mucosal cells and remission of leukoplakias resulted following a 3- to 6-month treatment. The development of new leukoplakias was also inhibited. The various endpoints differed in degree and time course to the administration of beta-carotene and vitamin A. Following termination of the beta-carotene or vitamin A administration, micronucleated cells and leukoplakia recurred in the oral cavity of chewers who continued this habit throughout the trial period. Attempts were made to maintain the protective effect achieved by the treatment with relatively high doses of the chemopreventive agents. Vitamin A given at a level of 50,000 IU/week was able to keep the frequency of micronucleated mucosal cells at low levels for at least a 12-month post-treatment period, whereas beta-carotene administered at 60 mg/week was less effective in maintaining the protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)