Detection of Point Mutations in Mammalian Sperm

Abstract

Our ability to assess the extent and significance of genetic damage resulting from exposure to environmental agents is limited. For the human population the two most important types of transmissible genetic damage are chromosomal aberrations and gene mutations. Established techniques are use routinely to detect chromosomal aberrations, but there are only a few established methods for the detection of point mutations. Any assessment of mutation frequency in potentially exposed humans is also complicated by family size, privacy considerations, and other sampling difficulties. Transmissible mutation frequency after exposure to a chemical agent can be measured by analyzing the offspring of the exposed individuals, or the possibility that genetic damage has occurred can be estimated by analyzing the cells of the exposed person. Methods for the detection of mutations in single cells from exposed individuals are under development. One such method is based on detection of thioguanine-resistant lymphocytes (1; see Albertini, these proceedings), and another is based on detection of variant hemoglobin types in single red blood cells by use of fluorescent antibodies (2). However, since germinal cells have singular relevance for the next generation, it would be beneficial to have a system for detection of point mutations directly in sperm. We have begun to develop such a system in laboratory animals and out goal is to examine similar techniques that might be applicable to the human population.