Dose-response relationship, kinetics of formation, and persistence of S-[2-(N7-guanyl)-ethyl]glutathione-DNA adduct in livers of channel catfish (Ictalurus punctatus) exposed in vivo to ethylene dichloride

Abstract

Formation of DNA adducts by reactive chemicals or their metabolites are often a precursor of mutagenesis and other adverse effects. Studies in juvenile channel catfish (Ictalurus punctatus) were conducted to determine the dose-response, kinetics of formation, and persistence of S-[2-(N7-guanyl)ethyl]glutathione hepatic-DNA adducts following a 4-h in vivo aqueous exposure to ethylene dichloride (EDC) at several dose levels. S-[2-(N7-guanyl)ethyl] glutathione adducts were detectable in liver tissue after 2 h of exposure and were still detectable three weeks after a single pulse exposure (detection limit=approximately 10 fmol, approximately 1 DNA adduct in 10(7) bases). Pretreatment of catfish with the glutathione-depleting agent diethylmaleate significantly reduced the level of tissue glutathione levels and, as a result, DNA adducts were not detected in pretreated fish. Catfish may serve as a useful sentinel species for detecting DNA-reactive chemicals in aquatic systems.