Genetic Toxicology of the Human: The Current Status of Somatic Gene Mutation.

摘要

The four currently available methods for evaluating human somatic gene mutation are described briefly and compared in terms of background frequencies, types of genetic lesion to which they respond, age structure, persistence, and responses to radiation, chemotherapy and smoking. The ensemble is then considered with regard to biomonitoring and carcinogenesis by reviewing specifically the collective capability to function as a dosimeter for environmental mutagens, as detectors of persons with DNA repair deficiencies, as a predictor of cancer, and as a general tool for human risk assessment. Clearly, additional methods are needed to cover beyond lymphocytes and erythrocytes, and to provide a full spectrum of persistence, availability, ease of use and coverage of genetic lesion. The methods already can function as rough population dosimeters, but display large inter-person variability that is not yet understood well enough to allow reasonable individual dosimetry. Several of the important human recessive repair deficiencies cause major increases in mutant frequencies. They are readily detectable by these methods in their homozygous form, but so far are not detectable when heterozygotic. Prediction of cancer has yet to be demonstrated with these methods. The data, however, are very sparse and should be expanded considerably in the near future. Also it is premature to evaluate these fledging methods for human risk assessment and environmental carcinogenesis. 25 refs.