Mutation spectra in Salmonella TA98, TA100, and TA104 of two phenylbenzotriazole mutagens (PBTA-1 and PBTA-2) detected in the Nishitakase River in Kyoto, Japan.
Previous studies have identified two potent aromatic amine mutagens in the Nishitakase River, a tributary of the Yodo River, which serves as the main drinking water supply for the Osaka area in Japan. The two potent mutagens are 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-am ino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[N-(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5- amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2). PBTA-1 and PBTA-2 are presumed to be formed from azo dyes discharged in a reduced form from dye factories to sewage treatment plants where they become chlorinated and are then discharged into the river. PBTA-1 and PBTA-2 account for 21% and 17% of the mutagenic activity of the Nishitakase River, respectively. Here we determined the mutation spectra induced by these two mutagens in TA98, TA100, and TA104 at 30-35, 8-10, and 2x, respectively, above the background. In TA98, the PBTA compounds produced identical mutation spectra, with 100% of the revertants containing the hotspot 2-base deletion of CG within the (CG)(4) sequence. In TA100, 73% of the revertants were GC-->TA transversions, with most of the remaining being GC-->AT transitions; the spectra produced by the two compounds in TA100 were not significantly different (p=0.8). In TA104, as in TA100, the majority (83%-87%) of the revertants were GC-->TA transversions, with most of the remaining revertants (11%-13%) being AT-->TA transversions. Thus, 83%-87% of the mutations induced by the PBTA compounds in TA104 were at G/C sites. The mutation spectra produced by the two compounds in TA104 were not significantly different (p0.08). PBTA-1 and PBTA-2 are structurally similar and have similar mutagenic potencies and mutation spectra in the respective strains. The mutation spectra produced by the PBTA compounds (100% hotspot deletion in TA98 and primarily GC-->TA transversions in TA100 and TA104) are similar to those produced by other potent aromatic amines, which is the class of compounds from which the PBTA mutagens derive.
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Department of Food and Nutrition Science, Kyoto Women's University, Kyoto, Japan.
Shaughnessy
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DT
Landi
S
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Terao
Y
Y
Sawanishi
H
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Nukaya
H
H
Wakabayashi
K
K
DeMarini
D M
DM
D020029:Base Pairing; D004269:DNA, Bacterial / Q000235:genetics; D005618:Fresh Water / Q000032:analysis; D007564:Japan; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000032:analysis*; D009154:Mutation; D012475:Salmonella / Q000187:drug effects / Q000235:genetics*; D014230:Triazoles / Q000032:analysis*; D014877:Water Pollution, Chemical / Q000032:analysis*
C115463:2-(2-(acetylamino)-4-(N-(2-cyanoethyl)ethylamino)-5-methoxyphenyl)-5-amino-7-bromo-4-chloro-2H-benzotriazole; C112866:2-(2-(acetylamino)-4-(bis(2-methoxyethyl)amino)-5-methoxyphenyl)-5-amino-7-bromo-4-chloro-2H-benzotriazole; D004269:DNA, Bacterial; D009153:Mutagens; D014230:Triazoles