Effect of a mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolizing enzymes in rat liver

J Environ Pathol Toxicol Oncol. 1994;13(3):163-8.

Abstract

The level of 8-OH-2-deoxyguanosine in rat liver DNA was measured as an index of oxidative damage after treating rats for 10 days at a dose ranging from 0.75 to 10 mg/kg with a mixture of 15 pesticides (dithiocarbamate, benomyl, thiabendazole, diphenylamine, chlorthalonil, procimidone, methidathion, chlorpyrifos-ethyl, fenarimol, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos-ethyl) commonly found in foods of central Italy. At the doses of 0.75 and 1 mg/kg DNA levels of 8-OH-2-deoxyguanosine were significantly increased relative to controls, whereas at higher doses (2.5, 5, 10 mg/kg) the levels returned to control values. The administration of the pesticide mixture dose dependently reduced benzo(a)pyrene hydroxylase, N-demethylase activities, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and thiol transferase activities in the liver. The results show that the pesticide mixture induced free radical DNA damage at low doses. However, at higher doses it produced a depression of cellular metabolism, inhibiting a further expression of oxidative damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • DNA / drug effects*
  • DNA / metabolism
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / metabolism
  • Enzymes / metabolism*
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Pesticides / metabolism
  • Pesticides / pharmacology*
  • Rats
  • Rats, Wistar
  • Xenobiotics / metabolism*

Substances

  • Enzymes
  • Pesticides
  • Xenobiotics
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Deoxyguanosine