Response of the Muta mouse lacZ/galE- transgenic mutation assay to DMN: comparisons with the corresponding Big Blue (lacI) responses.
The lacZ Muta mouse transgenic mutation assay was recently adapted into a selective assay based on use of E. coli galE(-) bacteria and phenyl galactoside (p-gal). A preliminary assessment of this selective assay was undertaken using a single oral dose of 10 mg/kg of dimethyl nitrosamine (DMN). The livers of treated male mice were assessed for UDS 2 h after dosing, and for lacZ- mutations 7, 11 and 20 days after dosing. A strong UDS response was recorded and a clear mutagenic response was observed at each of the 3 timepoints. Comparison of these data with earlier data derived using the Big Blue (lacI) mutation assay reveals a marginally greater sensitivity to DMN of the selective Muta mouse assay, an effect probably related to a biochemical difference between the strains of animal, as evidenced by the larger UDS response seen in the Muta mouse system. The original Muta mouse assay protocol was impractical. The galE- adaption makes the assay emminently practical and cost-effective. We are continuing to assess the true role of both the Big Blue assay and the galE- Muta mouse assay in mutagenicity/carcinogenicity prediction. The former assay enables access to B6C3F1 mice and F344 rats, the latter enables the rapid acquisition of data.
Tinwell
H
H
Zeneca Central Toxicology Laboratory, Nr. Macclesfield, Ches, UK.
Lefevre
P A
PA
Ashby
J
J
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics; D007763:Lac Operon; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D051381:Rats; D013045:Species Specificity
D004247:DNA; D004128:Dimethylnitrosamine