Dominant-lethal mutations and heritable translocations in mice

Conference · Sat Jan 01 04:00:00 EST 1983

OSTI ID:6146087

Generoso, W M

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
• Country of Publication: United States
• Language: English

Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
CELL CYCLE
CHROMOSOMAL ABERRATIONS
DNA
GERM CELLS
LETHAL MUTATIONS
MAMMALS
MICE
MOLECULAR BIOLOGY
MUTAGENS
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RADIOINDUCTION
RODENTS
TRANSLOCATION
VERTEBRATES