Adenosine kinase deficiency in tritiated deoxyadenosine-resistant mouse S49 lymphoma cell lines.
Mutant sublines were derived of S49 mouse T-lymphoma cells that were resistant to tritiated deoxyadenosine. Twenty-five isolates that were selected in 1 microCi/ml of the nucleoside were cross-resistant to 6-thioguanine, were sensitive to HAT (hypoxanthine, aminopterin, and thymidine), and contained less than 1% of hypoxanthine phosphoribosyltransferase activity in wild-type cells. One of the mutant clones, S49-dA2, was further subjected to selection in a medium containing 2 microCi/ml tritiated deoxyadenosine and 1 microgram/ml deoxycoformycin, an inhibitor of adenosine deaminase. All resistant subclones were cross-resistant to tubercidin, 6-methylmercaptopurine riboside, and arabinosyladenine. One of the subclones, S49-12, was completely devoid of adenosine kinase and was partially deficient in deoxyadenosine kinase. This subclone, however, contained wild-type levels of deoxycytidine kinase. DEAE chromatography of the wild-type cell extracts revealed two deoxyadenosine phosphorylating activities, one of which coeluted with adenosine kinase and was the enzyme missing in S49-12. The other species phosphorylated both deoxyadenosine and deoxycytidine, of which deoxycytidine was the preferred substrate.
Sastry
K J
KJ
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Huang
C
C
Chan
T S
TS
D000248:Adenosine Kinase / Q000172:deficiency*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003839:Deoxyadenosines / Q000494:pharmacology*; D003842:Deoxycytidine Kinase / Q000378:metabolism; D004351:Drug Resistance; D008223:Lymphoma / Q000201:enzymology; D051379:Mice; D009154:Mutation; D010770:Phosphotransferases / Q000172:deficiency* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor); D014316:Tritium
D003839:Deoxyadenosines; D014316:Tritium; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000248:Adenosine Kinase; D003842:Deoxycytidine Kinase; C020005:deoxyadenosine kinase