Mutagenicity of dipyridyls and their methylated derivatives in Salmonella typhimurium/rat liver microsome system.
The Salmonella/microsome assay with strains TA97, TA98, TA100, TA1535, TA1537 and TA1538 was used to examine the potential mutagenicity of 5 dipyridyls, 1 tripyridyl, 3 dipyridinium diiodides and 2 pyridinium monoiodides. The widely used herbicide paraquat (1,1-dimethyl-4,4'-dipyridinium diiodide) and its precursor 4,4'-dipyridyl gave weak and marginal mutagenic activity to Salmonella typhimurium TA1535 and TA1538 in the presence of S9-mix. Significantly high mutagenicity was obtained with 2,2'-, 3,3'-, 2,3'-, and 2,4'-dipyridyls, 2,2',2"-tripyridyl, and 5 pyridinium salts under the same conditions. The positive mutagenic response of 2,2',2"-tripyridyl suggests that higher polymers of pyridine contaminating paraquat preparations might be mutagenic. The dose-response curves of 1,1-dimethyl-3,3'-dipyridinium diiodide and 1,1'-dimethyl-2,2'-dipyridinium diiodide revealed an exponential relationship between the number of induced revertants and the compound concentrations. The results suggested that the mechanism of mutation induced by these two compounds might be attributed to the chain reactions of their free-radicals with molecular oxygen.
Lin
J K
JK
Institute of Biochemistry, College of Medicine National Taiwan University, Taipei, Republic of China.
Huang
I H
IH
Lee
K W
KW
Lin-Shiau
S Y
SY
D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics; D010269:Paraquat / Q000493:pharmacokinetics / Q000633:toxicity; D011725:Pyridines / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics
D009153:Mutagens; D011725:Pyridines; D010269:Paraquat