EFFECT OF ETHANOL ON PARAQUAT TOXICITY IN F344 RATS

The potential modifying effects of ethanol and paraquat on lesion deve lopment in livers and lungs of male F344 rats were studied. Animals we re divided into diethylnitrosamine (DEN)-initiated and non-initiated g roups, subgroups of each being exposed to 10 ml 20% ethanol/kg body we ight, 2.5 or 10 mg paraquat/kg body weight or a combination of 10 ml 2 0% ethanol/kg body weight and 2.5 or 10 mg paraquat/kg body weight, gi ven by intragastric intubation three times a week. Controls received 1 0 ml saline/kg body weight. All animals were subjected to two-thirds p artial hepatectomy at the end of wk 3 and killed at the end of wk 8. A ll five rats receiving 10 mg paraquat/kg body weight without DEN-pretr eatment died before termination of the experiment, but the additional ethanol treatment saved animals: only one of five rats died. Rats admi nistered 2.5 or 10 mg paraquat/kg body weight demonstrated lung toxici ty, as evidenced by fibrosis and hyperplasia, but not when simultaneou sly treated with ethanol in DEN-pretreated groups. In the liver, howev er, evaluation of glutathione S-transferase placental form (GST-P)-pos itive foci did not reveal any influence of the treatments on lesion de velopment in DEN-initiated animals. It is concluded that ethanol decre ases paraquat toxicity, and that neither agent, alone or in combinatio n, exerts any hepatocarcinogenic modification potential.