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Carcinogen-metabolizing enzymes and insecticides.

Salah A Sheweita1

  • 1Department of Bioscience and Technology, Institute of Graduate Studies and Research, Alexandria University, Egypt. sheweita@hotmail.com

Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
|December 29, 2004
PubMed
Summary

Common insecticides alter key liver enzymes involved in detoxification. This modification of the cytochrome P450 system by pesticides may increase the toxicity of environmental carcinogens.

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Area of Science:

  • Environmental Toxicology
  • Biochemistry
  • Pharmacology

Background:

  • The cytochrome P450 system and glutathione S-transferase enzymes are crucial for metabolizing xenobiotics.
  • Insecticides are widely used, and their impact on these detoxification systems requires thorough investigation.

Purpose of the Study:

  • To investigate the effects of common insecticides on Phase I (cytochrome P450 system) and Phase II (glutathione S-transferase) drug-metabolizing enzymes in male mice.
  • To assess the impact of single and repeated doses of specific insecticides on enzyme activities and glutathione levels.

Main Methods:

  • Male mice were orally administered single or repeated doses of insecticides: sumithion, dursban, chlordane, methoxychlor, heptachlor epoxide, and lindane.
  • Hepatic levels of cytochrome P450, cytochrome b5, NADPH-cytochrome c reductase, aryl hydrocarbon hydroxylase (AHH), N-nitrosodimethylamine N-demethylase I (NDMA-dI), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione (GSH) were measured.

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Main Results:

  • Repeated doses of sumithion, dursban, chlordane, methoxychlor, and heptachlor epoxide significantly decreased cytochrome P450 content, AHH, and NDMA-dI activities.
  • Lindane induced cytochrome P450, cytochrome b5, and AHH activities, while decreasing GSH levels and inducing GST activity.
  • Chlordane, methoxychlor, and heptachlor epoxide decreased GSH levels and GST activity, with varying effects on GR activity depending on the dose regimen.

Conclusions:

  • Insecticides significantly modify the activity of cytochrome P450-mediated drug oxidation and glutathione S-transferase systems.
  • These alterations in detoxification pathways can potentially enhance the toxicity and carcinogenicity of environmental pollutants like polycyclic aromatic hydrocarbons and N-nitrosodimethylamine (NDMA).