Involvement of adenosine kinase in the phosphorylation of formycin B in CHO cells.
In Chinese hamster ovary cells, [3H]formycin B is metabolized into formycin B-5'-monophosphate, formycin A-5'-monophosphate and higher phosphorylated derivatives of formycin A which are incorporated into RNA. Mutants of CHO cells independently selected for resistance to various adenosine analogs viz. toyocamycin, tubercidin, 6-methylmercaptopurine riboside, which contain no detectable activity of adenosine kinase (AK) in cell extracts, all exhibited between 2- to 3-fold increased resistance to formycin B. Formycin B-resistant mutants of CHO cells are also affected in AK, as indicated by the absence of AK activity in cell extracts. Both types of AK- mutants showed reduced uptake and phosphorylation of [3H]formycin B in comparison to the parental (AK+) cells. In addition, toxicity of formycin B towards CHO cells was reduced in presence of adenosine in a concentration dependent manner. These observations strongly indicate that in CHO cells, formycin B is phosphorylated via AK and that like other nucleoside analogs its phosphorylation may be essential for the drugs cellular toxicity.
Mehta
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KD
Gupta
R S
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D000241:Adenosine / Q000494:pharmacology; D000248:Adenosine Kinase / Q000235:genetics / Q000378:metabolism*; D000577:Amides; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004351:Drug Resistance; D005260:Female; D005573:Formycins / Q000378:metabolism*; D008778:Methylthioinosine / Q000494:pharmacology; D009154:Mutation; D010053:Ovary / Q000201:enzymology*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011720:Pyrazoles; D012263:Ribonucleosides / Q000494:pharmacology; D012266:Ribose; D014127:Toyocamycin / Q000494:pharmacology; D014372:Tubercidin / Q000494:pharmacology
D000577:Amides; D000903:Antibiotics, Antineoplastic; D005573:Formycins; D011720:Pyrazoles; D012263:Ribonucleosides; C034561:formycin B; D008778:Methylthioinosine; C002997:pyrazofurin; C034550:formycin; D012266:Ribose; D010770:Phosphotransferases; D000248:Adenosine Kinase; D000241:Adenosine; D014127:Toyocamycin; D014372:Tubercidin