The delayed genotoxic effect of N-nitroso N-propoxur insecticide in mammalian cells.
The N-nitroso derivative of an extensively used insecticide, propoxur, consistently induced dose-responsive chromosome aberrations and sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO-W8) cells. Further investigations indicated that post-treatment incubation with a regular 1.5-cell-cycle period did not offer an unbiased estimation of the genotoxicity of N-nitroso carbamate insecticides. The scale of chromosome aberration induction increased with extension of the post-treatment incubation period. Comparable phenomena were not found in CHO-AGT cells proficient for O(6)-methylguanine-DNA-methyltransferase. In CHO-W8 cells, pulsed-treatment of the insecticide in the 1st replication cycle showed higher SCE induction than in the 2nd cycle. Similar phenomenon was also found in SCE induced by N-nitroso derivatives from other carbamate insecticides including aldicarb, carbofuran and methomyl. Treated cells did not show significantly perturbed cell cycle progression until 12 h after treatment removal. Based on the above observations, the O(6)-methylguanine-DNA adduct is suggested to be the major lesion caused by the delayed genotoxic effect of N-methyl carbamate insecticides as described in this report.
Lin
Chih-Min
CM
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Wei
L Y
LY
Wang
Tsing-Cheng
TC
D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D007306:Insecticides / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D001074:Propoxur / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D007306:Insecticides; D009153:Mutagens; D001074:Propoxur