Genetic alterations in carcinogenesis and chemoprevention.

Laboratory and clinical studies suggest that genetic change is intrinsically involved in the development of cancer and that this change occurs in humans throughout carcinogenesis, in both early and late stages. Therefore, the quantification of the level of genetic change in human epithelial tissues may serve as a marker for cancer risk. The micronucleus test has been used to quantify the level of site-specific chromosomal breakage occurring in epithelial tissues of individuals at elevated risk for cancer. These studies include individuals exposed to carcinogens, patients who have chromosome-breakage syndromes, and individuals with premalignant lesions. As a counterpart to this approach, the assay has been used to study the suppression of this breakage with chemopreventive agents, some of which occur naturally in the diet. These agents include beta-carotene, retinyl palmitate, 13-cis-retinoic acid, riboflavin, canthaxanthin, and folic acid. Not all of these agents were effective. The success of the treatment depended on both the agent being used and the population being studied. The results of these studies suggest that successful intervention with chemopreventive agents will depend on tailoring treatment regimens to specific populations. The micronucleus test can be used along with other biological end points to obtain an early indication of the efficacy of chemopreventive agents in altering biological changes associated with carcinogenesis in tissues of high-risk individuals.