DIFFERENT RESPONSES OF RAT-LIVER ADENOSINE METABOLIZING ENZYMES DURING IN-VIVO AND IN-VITRO TREATMENT WITH INTERFERON-ALPHA-2B

Interferon-2 alpha b (IFN-alpha 2b) can exert antiproliferative activi ty in both normal and maligant liver tissue. To study mechanisms of it s antiproliferative action, the activity of the enzymes of adenosine m etabolism were investigated. We studied 5'-nucleotidase (an adenosine- producing enzyme) and adenosine deaminase (involved in adenosine degra dation). Female Wistar rats (3 weeks old) were treated with IFN-alpha 2b for 48 h, as were adult rats (3 months old) and adult rats subjecte d to partial hepatectomy. During IFN-a2b administration, the activity of 5'-nucleotidase increased in the liver of 3-week-old rats, proporti onately more than in adult rats, but the greatest increase was seen in partially hepatectomised rats. The activity of adenosine deaminase de creased in the liver of 3-week-old rats, did not change significantly in 3-month-old rats, but was significantly lower in partially hepatect omised rats. As high adenosine concentrations are toxic for mammalian cells, especially during proliferation, the progressive increase of ad enosine production, together with the progressive decrease of its degr adation, could be one of the mechanisms of IFN-alpha 2b-induced antipr oliferative activity. In vitro studies were performed using collagenas e-isolated hepatocytes. They were exposed to IFN-alpha 2b, a cAMP anal ogue, or both. The incubation of hepatocytes with IFN-alpha 2b did not significantly change the activity of both enzymes, whereas incubation with the cAMP analogue decreased 5'-nucleotidase activity and increas ed adenosine deaminase activity. The mechanism of IFN-alpha 2b-induced alteration in adenosine metabolism is therefore unclear.