Chemopreventive trials with vitamin A and beta-carotene: some unresolved issues

The administration of beta-carotene (180 mg/week) plus vitamin A (100,000 IU/week) or vitamin A alone (200,000 IU/week) to chewers of betel quids in Kerala, India led to a reduction in the frequency of micronucleated buccal mucosal cells, a remission of oral leukoplakia, and an inhibition of the development of new leukoplakias. The advantages of this test system include a profound knowledge of exposure levels to tobacco-specific nitrosamines, areca nut-specific nitrosamines, and reactive oxygen species (ROS)-generating polyphenolics; the ease of quantitating micronuclei in exfoliated buccal mucosal cells and oral leukoplakia by noninvasive procedures; and solid information on the incidence of preneoplastic lesions and carcinomas. Some practical issues such as the level of nontoxic beta-carotene which could maintain the reduced frequency of micronucleated cells and the remission of oral leukoplakias for prolonged periods of time, the logistics of distributing beta-carotene to the many millions of smokeless tobacco users who are at elevated risk for oral cancer, and the possibility of using beta-carotene in the form of sweet potatoes or red palm oil, which could contain an economical source of beta-carotene for developing countries in which most of the tobacco chewers live, still remain unresolved.