Enhanced mutagenicity of anisidine isomers in bacterial strains containing elevated N-acetyltransferase activity.
In previous studies on the mutagenicity of anisidine isomers, the ortho isomer was considered to be mutagenic towards standard Ames tester strains, while the para isomer gave equivocal results. In the present study we show that both para- and ortho-anisidine isomers are mutagenic in a Salmonella typhimurium tester strain containing elevated levels of N-acetyltransferase (YG1029). p-Anisidine gave a positive mutagenic response using either hamster S9 or ram seminal vesicle microsomes (RSVM) as an activating system, while o-anisidine gave a positive response only with the hamster S9 fraction. The mutagenic response from p-anisidine was greater than with o-anisidine in each case. In tests with p-anisidine and RSVM, the addition of arachidonic acid was not necessary to observe a mutagenic response. Catalase produced a dose-dependent decrease in the mutagenic response with p-anisidine and RSVM; this indicates that endogenous hydrogen peroxide from the bacteria acts as a substrate for the peroxidase activity of RSVM prostaglandin H synthase. These results demonstrate that both anisidine isomers are mutagenic and that N-acetyltransferase enzymes play an important role in their metabolism to mutagenic species.
Thompson
D C
DC
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Josephy
P D
PD
Chu
J W
JW
Eling
T E
TE
D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D008861:Microsomes / Q000187:drug effects; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010084:Oxidation-Reduction; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology*; D012602:Scopolamine Derivatives / Q000633:toxicity*; D012680:Sensitivity and Specificity
D002273:Carcinogens; D009153:Mutagens; D012602:Scopolamine Derivatives; D001191:Arylamine N-Acetyltransferase; C012183:anisodine