Puapairoj P, Cui L, Ogawa K, Akagi K, Hasegawa R, Ito N
First Department of Pathology, Nagoya City University Medical School, Japan.
Food Chem Toxicol. 1994 Apr;32(4):379-86. doi: 10.1016/0278-6915(94)90077-9.
The potential modifying effects of ethanol and paraquat on lesion development in livers and lungs of male F344 rats were studied. Animals were divided into diethylnitrosamine (DEN)-initiated and non-initiated groups, subgroups of each being exposed to 10 ml 20% ethanol/kg body weight, 2.5 or 10 mg paraquat/kg body weight or a combination of 10 ml 20% ethanol/kg body weight and 2.5 or 10 mg paraquat/kg body weight, given by intragastric intubation three times a week. Controls received 10 ml saline/kg body weight. All animals were subjected to two-thirds partial hepatectomy at the end of wk 3 and killed at the end of wk 8. All five rats receiving 10 mg paraquat/kg body weight without DEN-pretreatment died before termination of the experiment, but the additional ethanol treatment saved animals: only one of five rats died. Rats administered 2.5 or 10 mg paraquat/kg body weight demonstrated lung toxicity, as evidenced by fibrosis and hyperplasia, but not when simultaneously treated with ethanol in DEN-pretreated groups. In the liver, however, evaluation of glutathione S-transferase placental form (GST-P)-positive foci did not reveal any influence of the treatments on lesion development in DEN-initiated animals. It is concluded that ethanol decreases paraquat toxicity, and that neither agent, alone or in combination, exerts any hepatocarcinogenic modification potential.
研究了乙醇和百草枯对雄性F344大鼠肝脏和肺部损伤发展的潜在调节作用。动物被分为二乙基亚硝胺（DEN）启动组和未启动组，每组再分为亚组，分别接受10 ml 20%乙醇/千克体重、2.5或10 mg百草枯/千克体重，或10 ml 20%乙醇/千克体重与2.5或10 mg百草枯/千克体重的组合，每周经胃内插管给药三次。对照组接受10 ml生理盐水/千克体重。所有动物在第3周结束时接受三分之二部分肝切除术，并在第8周结束时处死。所有五只接受10 mg百草枯/千克体重且未进行DEN预处理的大鼠在实验结束前死亡，但额外的乙醇处理挽救了动物：五只大鼠中只有一只死亡。给予2.5或10 mg百草枯/千克体重的大鼠表现出肺毒性，表现为纤维化和增生，但在DEN预处理组中同时用乙醇处理时则未出现。然而，在肝脏中，对谷胱甘肽S-转移酶胎盘型（GST-P）阳性灶的评估未发现这些处理对DEN启动动物的损伤发展有任何影响。得出的结论是，乙醇可降低百草枯毒性，且两种药物单独或联合使用均无任何肝癌发生修饰潜能。
