DNA target sites associated with chemical induction of dominant-lethal mutations and heritable translocations in mice

Technical Report · Sat Jan 01 04:00:00 EST 1983

OSTI ID:5463991

Generoso, W M; Cain, K T; Cornett, C C; Cacheiro, N L.A.

In male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant lethals and heritable translocations effectively while others induce primarily dominant lethals. Production of these two endpoints appears to be determined by the stability of alkylation products in chromosomes. If reaction products are intact in male chromosomes at the time of sperm entry, they maybe repaired in fertilized eggs, or else, they persist to the time of pronuclear chromosome replication and lead to chromatid-type aberrations and lethality. Production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. These are then converted into chromosome exchanges (both symmetrical and asymmetrical) after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type aberration). Thus, dominant lethals result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. Heritable translocations appear to be associated with alkylation at the nitrogen positions and dominant lethals with alkylation at various sites, including nitrogen and oxygen of bases and of the phosphate backbone.

• Research Organization: Oak Ridge National Lab., TN (USA)
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5463991
• Report Number(s): CONF-831258-3; ON: DE84004544
• Country of Publication: United States
• Language: English

Related Subjects

551000 -- Physiological Systems
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALKYLATING AGENTS
AMINES
ANIMALS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
CARBONIC ACID DERIVATIVES
CHROMOSOMAL ABERRATIONS
DATA
DNA ADDUCTS
DOMINANT MUTATIONS
EMS
EPOXIDES
ESTERS
EXPERIMENTAL DATA
GAMETES
GERM CELLS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFORMATION
LETHAL MUTATIONS
MAMMALS
MATING
METHYL METHANESULFONATE
METHYL NITROSOUREA
MICE
MUTAGENS
MUTATIONS
NITROSO COMPOUNDS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PURINES
RODENTS
SPERMATOZOA
SULFONIC ACID ESTERS
VERTEBRATES