Effects of 2'-deoxyadenosine, 9-beta-D-arabinofuranosyladenine, and related compounds on S-adenosyl-L-homocysteine hydrolase activity in synchronous and asynchronous cultured cells
Cass, C.E.; Selner, M.; Ferguson, P.J.; Phillips, J.R.
Cancer Research 42(12): 4991-4998
1982
ISSN/ISBN: 0008-5472 PMID: 6982751 Document Number: 187003
Inhibition of S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) (adenosylhomocysteinase) has been suggested as contributing to the cytotoxic effects of 2'-deoxyadenosine and 9-.beta.-D-arabinofuranosyladenine (ara-A). In the current work, the activity of adenosylhomocysteinase in extracts of asynchronous HeLa S3 cells and Chinese hamster ovary cells under saturating conditions for both substrates (adenosine, L- homocysteine). Adenosylhomocysteinase activity did not change in either cell type as cells progressed from G1 through S phase of the replication cycle. The relationship between cytotoxicity and the cell cycle was assessed for both adenosylhomocysteinase-inhibitory (ara-A) and noninhibitory (tubercidin, 9-.beta.-D-xylofuranosyladenine, and 3'-deoxyadenosine) agents. High concentrations of the ara-A prodrug, 9-.beta.-D-arabinofuranosyladenine 5'-monophosphate, were required to achieve cytotoxicity against synchronous HeLa cells, and there were no apparent differences in cytotoxicity between G1 and mid-S phase, suggesting that ara-A is not strongly phase specific. 9-.beta.-D-Xylofuranosyladenine was somewhat more toxic during S phase than G1 phase, and tubercidin and 3'-deoxyadenosine exhibited similar toxicities.