TEMPERATURE-MODULATED CARCINOGENICITY OF 7,12-DIMETHYLBENZ[a]ANTHRACENE IN RAINBOW TROUT

Abstract

Temperature-modulated hepatic disposition, covalent binding of radiolabeled genotoxin to hepatic DNA, and cancer incidence in rainbow trout ( Oncorhyncus mykiss ) were assessed after a single exposure to 7,12-dimethylbenz[a]anthracene (DMBA). Fish (2 g) were acclimated at 10, 14, or 18°C for 1 mo and then exposed to 1 ppm DMBA in their water for 20 h. Exposures were at respective acclimation temperatures, or 10 and 18°C acclimated fish were shifted to 14°C for DMBA exposures. After 4 but not 20 h of exposure, hepatic [ 3 H]DMBA equivalents increased with temperature for fish exposed at their respective acclimation temperatures (10 or 18°C). Covalent binding of [ 3 H]DMBA to hepatic DNA was similar after 3 d in fish exposed at their respective acclimation temperatures. However, in fish exposed at 14°C, after 3 d the concentration of [ 3 H]DMBA covalently bound to hepatic DNA was higher in 10°C than 18°C acclimated fish. After 21 d, covalent binding of [ 3 H]DMBA to hepatic DNA was less persistent in 18°C than 10°C acclimated, exposed, and reared fish. There were no differences between temperature-shifted groups at that time. Temperature effects on tumor incidence were assessed 9 mo after DMBA waterborne exposures in fish that were reared at (1) their respective acclimation and exposure temperatures, (2) 14°C after exposure at their respective acclimation temperature, and (3) 14°C after 14°C exposures. Incidence of stomach, liver, and swimbladder cancer increased dramatically with rearing temperature. Differences in tumor incidence were less marked in fish reared at the same temperature (14°C). A strong negative correlation between liver tumor incidence and persistence of [ 3 H]DMBA equivalents covalently bound to hepatic DNA suggested increased error-prone DNA repair at warmer temperature played an important role in increased tumor incidence.