Expression of spermidine/spermine N1-acetyltransferase in growing Yoshida AH-130 hepatoma cells.
Activity and messenger RNA levels of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme of the polyamine interconversion pathway, were investigated in host liver and in Yoshida AH-130 ascites hepatoma cells as a function of tumor growth phases. Enzyme activity reached maximal values at day 10 in host liver (2.0-fold increase) and at days 10 and 14 in hepatoma cells (4.2- and 5.4-fold increases)--that is, when the cellular growth was nearly arrested. At day 10 the messenger RNA levels of spermidine/spermine N1-acetyltransferase were augmented concomitantly; they were about two and four times higher, respectively, in host liver and tumor cells than in control liver. The in vitro transcription rate seemed to be constant during hepatoma cell growth. Treatment of the animals with N1,N2-bis-(2,3-butadienyl)-1,4-butanediamine (MDL 72527), a specific inhibitor of polyamine oxidase, caused large accumulation of N1-acetylspermidine in hepatoma cells and in the ascitic fluid; the maximal values were reached at day 14. The levels of putrescine in inhibitor-treated rats decreased in hepatoma cells (day 5) and in ascitic fluid (days 5 and 14), whereas values of spermidine and spermine remained unchanged. The proposed role for spermidine/spermine N1-acetyltransferase-enhanced expression is to regulate the cellular polyamine pool by causing their excretion as acetylderivatives from tumor cells into the ascitic fluid, even if putrescine seems also to be excreted. Eventual repeat uptake of putrescine by hepatoma cells could contribute to the control of cellular polyamine levels.
Desiderio
M A
MA
Institute of General Pathology, University of Milan, Italy.
Bardella
L
L
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009368:Neoplasm Transplantation; D011073:Polyamines / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured / Q000637:transplantation; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D011073:Polyamines; D012333:RNA, Messenger; D000099228:Diamine N-Acetyltransferase