Different responses of rat liver adenosine metabolizing enzymes during in vivo and in vitro treatment with interferon-alpha 2b.
Interferon-alpha 2b (IFN-alpha 2b) can exert antiproliferative activity in both normal and malignant liver tissue. To study mechanisms of its antiproliferative action, the activity of the enzymes of adenosine metabolism were investigated. We studied 5'-nucleotidase (an adenosine-producing enzyme) and adenosine deaminase (involved in adenosine degradation). 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 subjected to partial hepatectomy. During IFN-alpha 2b administration, the activity of 5'-nucleotidase increased in the liver of 3-week-old rats, proportionately more than in adult rats, but the greatest increase was seen in partially hepatectomised rats. The activity of adenosine deaminase decreased in the liver of 3-week-old rats, did not change significantly in 3-month-old rats, but was significantly lower in partially hepatectomised rats. As high adenosine concentrations are toxic for mammalian cells, especially during proliferation, the progressive increase of adenosine production, together with the progressive decrease of its degradation, could be one of the mechanisms of IFN-alpha 2b-induced antiproliferative activity. In vitro studies were performed using collagenase-isolated hepatocytes. They were exposed to IFN-alpha 2b, a cAMP analogue, 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 increased adenosine deaminase activity. The mechanism of IFN-alpha 2b-induced alteration in adenosine metabolism is therefore unclear.
Kocić
G
G
Institute of Biochemistry, Faculty of Medicine Nis, Serbia, Yugoslavia.
Kocić
R
R
Vlahović
P
P
Pavlović
D
D
Jevtović
T
T
D015720:5'-Nucleotidase / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000242:Cyclic AMP; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase