ENHANCEMENT BY ETHYL-ALCOHOL OF EXPERIMENTAL HEPATOCARCINOGENESIS INDUCED BY N-NITROSOMORPHOLINE

The effects of ethyl alcohol (EtOH) during or after treatment with N-n itrosomorpholine (NNM) on hepatocarcinogenesis, ornithine decarboxylas e (ODC) activity and the labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containin g NNM for 8 weeks and received i.p. injections of I g EtOH/kg body wei ght every other day during or after treatment with NNM. Preneoplastic and neoplastic lesions staining positively for glutathione-S-transfera se, placental type (GST-P), were examined immunohistochemically. At th e end of experiment at week 16, administration of EtOH after NNM treat ment had no significant effect on the number and size of GST-P-positiv e hepatic lesions, whereas administration of EtOH during NNM treatment significantly increased the number and percentage area but not the me an area of GST-P-positive hepatic lesions. EtOH caused significant inc reases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and the adjacent hepatocytes after the cessati on of EtOH administration but not during EtOH treatment. Our findings indicate that EtOH enhances hepatocarcinogenesis and suggest that this effect may be closely related to the increases in ODC activity and ce ll proliferation in enzyme-altered lesions and the adjacent liver afte r EtOH treatment. (C) 1997 Wiley-Liss, Inc.