Differential sensitivity of RSVts (temperature-sensitive Rous-sarcoma virus)-infected rat kidney cells to nucleoside antibiotics at permissive and non-permissive temperatures.
Among a variety of anti-tumour agents tested, oxanosine and 5-azacytidine were found to be significantly more effective in inhibiting growth of rat kidney cells infected with a temperature-sensitive mutant of Rous sarcoma virus at a permissive temperature (33 degrees C) than at a non-permissive temperature (39 degrees C). These two nucleoside antibiotics were antagonistic to each other in cytotoxicity. They seem to share the same carrier-mediated membrane-transport system, because dipyridamole, a potent inhibitor of nucleoside transport, protected cells from the cytotoxicity of both drugs. Thymidine transport, which is twice as fast in cells at 33 degrees C as at 39 degrees C, was competitively inhibited by both drugs. Thus the differential toxicity of oxanosine and 5-azacytidine at the two temperatures is thought to be due to their increased transport via the thymidine-transport system, which is somehow under the influence of the active src-gene product.
Uehara
Y
Y
Hasegawa
M
M
Hori
M
M
Umezawa
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001374:Azacitidine / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D011687:Purines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D012263:Ribonucleosides / Q000627:therapeutic use; D001357:Sarcoma, Avian / Q000188:drug therapy*; D013696:Temperature
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D011687:Purines; D011743:Pyrimidines; D012263:Ribonucleosides; C032886:oxanosine; D001374:Azacitidine