DNA damaging activity of methyl parathion

Abstract

14C-methyl parathion was covalently bound to DNA, RNA and proteins of various rat and mouse organs 22 hr after i.p. injection. Covalent binding index (CBI) to liver DNA was low in both species and typical of weak initiators. The labelings of RNA and proteins from different organs of both species was slightly higher than DNA binding. No interaction with brain nucleic acids was observed (CBI detection limit: 2.8). The in vitro enzyme-mediated interaction of methyl parathion with calf thymus DNA was mainly performed by rodent liver microsomes and, to a lesser extent, by microsomes from mouse kidney and lung whereas brain microsomes were inefficient. Activation of methyl parathion by cytosolic fractions from different organs of both species to form(s) capable of binding to DNA was negligible. When microsomes and cytosolic fractions from rodent liver and lung or mouse kidney were simultaneously present in the incubation mixture, a synergistic effect in catalyzing DNA binding was observed. The extent of DNA binding was reduced by adding SKF 525-A to the microsomal standard incubation mixture, whereas it was enhanced by adding GSH to liver or lung murine microsomes or to mouse kidney microsomes. These results suggest that methyl parathion is bioactivated by P450-dependent microsomal mixed function oxidase system and by microsomal GSH-transferases. By contrast, cytosolic GSH- transferases play a detoxificant role in the metabolism of this compound.