Dimethylnitrosamine genotoxicity: does N-acetyltransferase activity play a role?
Dimethylnitrosamine (DMN) genotoxicity was evaluated in two test systems: induction of the umu operon (as measured by expression of a lacZ gene fusion) and mutagenicity (as measured by the Ames assay). Three Salmonella typhimurium strains were used; the strains differ in the level of expression of the enzyme acetyl CoA:arylamine N-acetyltransferase (NAT). We did not observe increased sensitivity in a strain with a plasmid-borne copy of the nat gene, and expressing very high levels of NAT activity. In contrast to a recent report, we conclude that NAT-dependent metabolic activation does not play a major role in the genotoxicity of this carcinogenic nitrosamine.
Josephy
P D
PD
Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.
Lord
H L
HL
Snieckus
V A
VA
D000873:Anthracenes / Q000633:toxicity; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000201:enzymology; D013045:Species Specificity
D000873:Anthracenes; C006593:2-anthramine; D001191:Arylamine N-Acetyltransferase; D004128:Dimethylnitrosamine