The effect of ethanol consumption on liver regeneration has been found to exert significant but inconsistent changes of several metabolic pathways. The present project examined the effect of chronic ethanol consumption on ornithine decarboxylase activity (ODC), polyamine biosynthesis and proto-oncogene expression in the rat liver after partial hepatectomy (PH). Chronic exposure to ethanol has been reported to increase both the activity and half- life of ODC, yet significantly inhibit post-hepatectomy DNA synthesis and restitution of liver mass. After using an established model of chronic ethanol feeding, animals underwent 2/3 partial hepatectomy and were sacrificed at 30 min, 1,3,6,12,18 and 24 hours thereafter. ODC activity increased significantly in both ethanol and pair-fed animals at 3 to 6 hours post-PH. However, the ethanol-treated group exhibited a fivefold less increase in activity as compared to the pair-fed animals. This decrease was paralleled by a similar change in putrescine activity, a major polyamine product of ODC activity. By 24 hours, ODC activity was similar in both groups. Total ODC protein content remained invariant to partial hepatectomy and/or chronic ethanol ingestion. In contrast, measurement of ODC mRNA levels revealed a tenfold increase at 12 and 24 hours but no significant difference between pair-fed and alcohol-treated animals. Examination of a number of proto-oncogenes including c-myc, c-fos, v-raf, H-ras, c-mos, and v-erb B revealed no significant differences in expression between the two groups. Similar results were noted when expression of multidrug resistant (MDR-I), albumin, alpha-fetoprotein, and glutathione S-transferase-P genes was examined. The mRNA levels of the ethanol-inducible cytochrome P-450 was slightly increased in the ethanol-treated animals. The results suggest that in the present model, chronic alcohol ingestion induces diminished ODC activity in the early time points post-PH without affecting ODC protein content or mRNA levels. Proto-oncogene expression appears to be invariant to chronic alcohol ingestion under the conditions described.
