Multiple mechanisms of adenosine toxicity in an adenosine sensitive mutant of baby hamster kidney (BHK) cells.
A class of arabinosyladenine-resistant baby hamster kidney (BHK) cell mutants, isolated in our laboratory, shows cross-resistance to deoxyadenosine, alteration of adenosine kinase, elevation of spontaneous mutation rate, and extreme sensitivity to adenosine. One of these adenosine sensitive mutants, ara-s10d, was isolated spontaneously and studies with Ador revertants suggest the involvement of a single pleiotropic mutation. The enhanced adenosine toxicity in ara-s10d cells can be attributed to pyrimidine nucleotide starvation and to at least one other mechanism, which is associated with a 200-fold elevation of IMP, 3-5 fold elevation of ATP, GTP, S-adenosylmethionine (AdoMet) and methylthioadenosine (MeSAdo).
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000248:Adenosine Kinase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003570:Cytidine Triphosphate / Q000378:metabolism; D003839:Deoxyadenosines; D004351:Drug Resistance; D006160:Guanosine Triphosphate / Q000378:metabolism; D007668:Kidney; D009154:Mutation; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D013872:Thionucleosides / Q000378:metabolism / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000378:metabolism; D014740:Vidarabine / Q000494:pharmacology
D003839:Deoxyadenosines; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D003570:Cytidine Triphosphate; D012436:S-Adenosylmethionine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D012435:S-Adenosylhomocysteine; D000248:Adenosine Kinase; D014740:Vidarabine; D000241:Adenosine; D014544:Uridine Triphosphate