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Published on: September 25, 2017
The delayed genotoxic effect of N-nitroso N-propoxur insecticide in mammalian cells
Chih-Min Lin1, L Y Wei, Tsing-Cheng Wang
1Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Abstract:
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.
Insights
N-nitroso propoxur causes DNA damage, leading to chromosome aberrations and sister-chromatid exchanges (SCEs) in cells. Extended incubation reveals delayed genotoxicity, suggesting O(6)-methylguanine-DNA adducts are key lesions.
Area of Science:
- Environmental toxicology
- Molecular toxicology
- Genetics
Background:
- Propoxur is a widely used carbamate insecticide.
- N-nitroso derivatives of carbamate insecticides can exhibit genotoxic effects.
- Understanding the mechanisms of genotoxicity is crucial for risk assessment.
Purpose of the Study:
- To investigate the genotoxicity of N-nitroso propoxur in Chinese hamster ovary (CHO) cells.
- To elucidate the role of O(6)-methylguanine-DNA-methyltransferase (MGMT) in mediating the genotoxic effects.
- To explore the influence of post-treatment incubation periods on genotoxicity assessment.
Main Methods:
- Exposure of CHO-W8 and CHO-AGT cells to N-nitroso propoxur.
- Assessment of chromosome aberrations and sister-chromatid exchanges (SCEs).
- Varying post-treatment incubation periods and pulsed-treatment exposure cycles.
Main Results:
- N-nitroso propoxur induced dose-responsive chromosome aberrations and SCEs in CHO-W8 cells.
- Extended post-treatment incubation increased chromosome aberration induction.
- CHO-AGT cells, proficient in MGMT, showed no comparable phenomena.
- Pulsed-treatment in the first replication cycle led to higher SCE induction than in the second cycle.
Conclusions:
- The O(6)-methylguanine-DNA adduct is implicated as the primary lesion responsible for the delayed genotoxic effects of N-methyl carbamate insecticides.
- Standard genotoxicity testing protocols may underestimate the risks associated with these compounds.
- MGMT status significantly influences cellular response to N-methyl carbamate genotoxicity.
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