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HISTORY OF GERM CELL MUTAGENESIS
Citation:
Preston, R J. HISTORY OF GERM CELL MUTAGENESIS. Presented at Assessing Human Germ Cell Mutagenesis in the Post-Genome Era: A Celebration of the Legacy of Bill Russell, Bar Harbor, ME, September 28-30, 2004.
Description:
Much of the early work on germ cell mutation analysis was conducted with nonmammalian species, but this historical overview will begin with the rodent studies that provided quantitative data on induced mutations. The initial studies of mutation induction utilized the newly developed mouse specific locus tester stocks for quantitating radiation-induced mutations. Data from Harwell, Oak Ridge and Neuherberg provided the mutation data for genetic risk assessments, for acute doses, chronic doses and multiple generation exposures. Much more recently the mutants developed from these early studies have been characterized at the molecular level. Based on this, it has been estimated that a majority of radiation-induced germ cell mutations are the result of genomic alterations that involve quite large segments of DNA (particularly deletions). The mutation frequency in mature and maturing oocytes following acute exposures is higher than for spermatogonia, but no radiation-induced mutations have been recovered from arrested oocytes. The dose-rate reduction factor is also greater for mature and maturing oocytes. Chromosomal translocations and dominant lethality (the result of chromosomal aberrations) have also been studied in rodent systems over several decades. In general, the response for reciprocal translocations with dose and for dose-rate reductions is similar to those for gene mutations in a qualitative sense, although not quantitatively. For both specific locus mutations and reciprocal translocations the mouse is a reasonable model for predicting effects in humans. Human radiation genetic risk assessment (as most currently defined by UNSCEAR) utilizes spontaneous human mutation data and radiation-induced mouse mutation data.