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Title: Dominant-lethal mutations and heritable translocations in mice

Conference ·
OSTI ID:6146087

Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

Research Organization:
Oak Ridge National Lab., TN (USA)
DOE Contract Number:
W-7405-ENG-26
OSTI ID:
6146087
Report Number(s):
CONF-830556-5; ON: DE83012656
Resource Relation:
Conference: International workshop on the principles of environmental mutagenesis, carcinogenesis, and teratogenesis, Shanghai, China, 25 May 1983
Country of Publication:
United States
Language:
English