El-Zahr Camille R, Zhang Quan, Hendricks Jerry D, Curtis Lawrence R
Department of Fisheries and Wildlife, Oregon State University, Corvallis, Oregon 97331, USA.
J Toxicol Environ Health A. 2002 Jun 14;65(11):787-802. doi: 10.1080/00984100290071072.
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.
在虹鳟鱼（Oncorhyncus mykiss）单次暴露于7,12-二甲基苯并[a]蒽（DMBA）后，评估了温度调节的肝脏处置、放射性标记的基因毒素与肝脏DNA的共价结合以及癌症发病率。将2克重的鱼在10℃、14℃或18℃下驯化1个月，然后在水中暴露于1 ppm的DMBA中20小时。暴露在各自的驯化温度下，或者将在10℃和18℃驯化的鱼转移到14℃进行DMBA暴露。在暴露4小时而非20小时后，在各自驯化温度（10℃或18℃）下暴露的鱼，肝脏中[³H]DMBA当量随温度升高而增加。在各自驯化温度下暴露3天后，[³H]DMBA与肝脏DNA的共价结合情况相似。然而，在14℃下暴露的鱼中，3天后共价结合到肝脏DNA上的[³H]DMBA浓度，在10℃驯化的鱼中高于18℃驯化的鱼。21天后，[³H]DMBA与肝脏DNA的共价结合在18℃驯化、暴露和饲养的鱼中比10℃的鱼更不持久。此时温度转移组之间没有差异。在DMBA水暴露9个月后，对在（1）各自驯化和暴露温度下饲养的鱼、（2）在各自驯化温度下暴露后在14℃饲养的鱼以及（3）在14℃暴露14℃后饲养的鱼，评估温度对肿瘤发病率的影响。胃、肝和鳔癌的发病率随饲养温度显著增加。在相同温度（14℃）下饲养的鱼中，肿瘤发病率的差异不太明显。肝脏肿瘤发病率与共价结合到肝脏DNA上的[³H]DMBA当量的持久性之间存在强烈的负相关，这表明在较高温度下易错DNA修复增加在肿瘤发病率增加中起重要作用。
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