Mutation studies with dimethyl nitrosamine in young and old lac I transgenic mice.
Young adult (approximately 8 w) and old (approximately 72 w) lac I transgenic mice have been exposed to a single oral dose of dimethyl nitrosamine (NDMA). 2.5 h later unscheduled DNA synthesis was observed in the liver of the young animals (19.5 NG; control value -3.4 NG). The frequency of lac I- mutations in the liver of the young animals was elevated 7, 10 and 20 days after dosing. A similar fold-increase in mutant frequency was seen 7 days after dosing the old animals. It is concluded that mutability of the genome of old animals is not significantly different to that of young animals. Aspects of the minimum Big Blue assay protocol are discussed, as are the differing perceptions of the role of the assay in carcinogen hazard assessment.
Tinwell
H
H
Zeneca Central Toxicology Laboratory, Alderley Park, Nr. Macclesfield, Ches., UK.
Lefevre
P A
PA
Ashby
J
J
D000367:Age Factors; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D004251:DNA Transposable Elements; D004128:Dimethylnitrosamine / Q000633:toxicity*; D005822:Genetic Vectors; D007763:Lac Operon / Q000187:drug effects*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation
D004251:DNA Transposable Elements; D009153:Mutagens; D004247:DNA; D004128:Dimethylnitrosamine