MICRONUCLEI - A POTENTIAL INTERMEDIATE MARKER FOR CHEMOPREVENTION OF AERODIGESTIVE TRACT CANCER

Because they may be used as a quantifiable estimate of the extent of r ecent DNA injury, micronuclei, extrachromosomal fragments of DNA, are among the most studied potential intermediate markers of cancer chemop revention. Serial measurements of micronuclei frequency may be easily performed on scrapings from the oral cavity or on bronchial brushings. Assessment of micronuclei frequency and its response to chemopreventi ve agents has been incorporated into studies of upper aerodigestive tr act and lung cancer chemoprevention. These studies have helped define the characteristics of micronuclei and have suggested a role for this test in future chemoprevention studies. Micronuclei frequency has been shown to be increased in the oral and bronchial mucosa of individuals with known carcinogen exposure and is higher at the site of the great est carcinogen exposure, such as the site where tobacco quids are held , than in grossly normal-appearing mucosa. Treatment with chemoprevent ive agents leads to a reduction in micronuclei frequency. In oral leuk oplakia studies, this effect followed treatment with beta-carotene, re tinol, alpha-tocopherol, and 13-cis-retinoic acid. The multistep proce ss of epithelial carcinogenesis results from DNA damage and specific g enetic events. That micronuclei reflect ongoing DNA injury suggests th e hypothesis that long term suppression of cellular genotoxicity, as r eflected by a reduction in micronuclei frequency, ultimately leads to a reduction in cancer incidence. (C) 1993 Wiley-Uss, Inc.