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

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-(N-7-guanyl)ethyl]glutathione hepatic-DNA adducts following a 4-h in vivo aqueous exposure to ethylene dichloride (EDC) at several dose levels. S-[2-(N-7-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 = similar to 10 fmol, similar to 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. Environ. Toxicol. Chem. 2010;29:1537-1544. (C) 2010 SETAC