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.

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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