DNA damage and repair in mouse embryos following treatment transplacentally with methylnitrosourea and methylmethanesulfonate
Mouse embryos were labeled in vivo at 10 1/2-12 1/2 days of gestation with (/sup 3/H)-thymidine and subjected to DNA damage using x-ray, methylmethanesulfonate, or methylnitrosourea. DNA damage and its repair were assessed in specific cell preparations from embryos isolated at intervals thereafter using the highly sensitive method of nucleoid sedimentation, which evaluates the supercoiled state of the DNA. Repair of x-ray damage was demonstrated using trypsin-dispersed cells from whole embryos and from homogenized embryonic liver to show the validity of the analytical approach. The effects of the highly teratogenic methylnitrosourea and the much less teratogenic methylmethanesulfonate were compared in the targeted limb buds using equitoxic doses of the two alkylating agents. DNA supercoiling was fully restored after 24 hr in limb bud cells damaged with methylmethanesulfonate, while as much as 48 hr were required for full repair of methylnitrosourea damage. These results demonstrated the feasibility of studying DNA repair in embryonic tissues after damage in vivo and suggest that the potency of methylnitrosourea as a teratogen may be correlated with a prolonged period required for complete repair of DNA.
- Research Organization:
- Univ. of South Alabama, Mobile
- OSTI ID:
- 5742165
- Journal Information:
- Teratog., Carcinog., Mutagen.; (United States), Vol. 4:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
EMBRYOS
DNA REPAIR
GENETIC RADIATION EFFECTS
METHYL METHANESULFONATE
TERATOGENESIS
NITROSOUREAS
ALKYLATING AGENTS
COMPARATIVE EVALUATIONS
DNA
IN VIVO
LIVER
MICE
THYMIDINE
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
X RADIATION
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
DIGESTIVE SYSTEM
ELECTROMAGNETIC RADIATION
ESTERS
GENETIC EFFECTS
GLANDS
HETEROCYCLIC COMPOUNDS
IONIZING RADIATIONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MUTAGENS
NITROSO COMPOUNDS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
RIBOSIDES
RODENTS
SULFONIC ACID ESTERS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
560152 - Radiation Effects on Animals- Animals