Temperature-modulated carcinogenicity of 7,12-dimethylbenz[a]anthracene in rainbow trout.
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 degrees 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 degrees C acclimated fish were shifted to 14 degrees 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 degrees 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 degrees C, after 3 d the concentration of [(3)H]DMBA covalently bound to hepatic DNA was higher in 10 degrees C than 18 degrees C acclimated fish. After 21 d, covalent binding of [(3)H]DMBA to hepatic DNA was less persistent in 18 degrees C than 10 degrees 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 degrees C after exposure at their respective acclimation temperature, and (3) 14 degrees C after 14 degrees 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 degrees 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.
El-Zahr
Camille R
CR
Department of Fisheries and Wildlife, Oregon State University, Corvallis, Oregon 97331, USA.
Zhang
Quan
Q
Hendricks
Jerry D
JD
Curtis
Lawrence R
LR
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D001822:Body Burden; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity*; D018736:DNA Adducts / Q000032:analysis; D004781:Environmental Exposure / Q000009:adverse effects; D015994:Incidence; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity; D013696:Temperature; D014018:Tissue Distribution; D014337:Trout / Q000378:metabolism*
D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene