Methyl nitrosourea induced unscheduled DNA synthesis in vivo in mice. Effects of background genotype on excision repair during aging.
We studied mice from five genetic strains at two ages (young, 10 +/- 0.49 weeks; old, 74.4 +/- 14 weeks) for the induction of unscheduled DNA synthesis (UDS) in bone marrow cells following in vivo challenge by a known mutagen and carcinogen: methyl nitrosourea (MNU). The data, in the form of mean silver grains/cell and the percentage of cells in UDS, were used to evaluate genotype (strain) dependent differences in response to mutagenic challenge and changes in this response with age in otherwise normal individuals. Increasing doses of MNU significantly increased both mean silver grains/cell and the percentage of cells in UDS. The increase was, however, strain specific. Furthermore, the older animals generally had both lower mean silver grains/cell and a smaller percentage of cells in UDS as compared to their younger counterparts. This reduction in UDS patterns during aging (aging response) was variable among mouse genotypes. We attribute these observations to subtle differences in the genetic backgrounds of the mice which affects both their ability to repair damage induced by MNU and the genotype specific decline in this ability with old age.
Bond
S L
SL
Department of Zoology, University of Western Ontario, London, Canada.
Singh
S M
SM
D000375:Aging / Q000235:genetics*; D000818:Animals; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004260:DNA Repair; D005838:Genotype; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D008770:Methylnitrosourea; D004247:DNA