Search for the biochemical parameters of tumor cell sensitivity and resistance to antimetabolites.
The metabolism of murine tumors sensitive and resistant to 6-theopurines and 5-fluorouracil (5-FU) was studied. A positive correlation between the tumor sensitivity to thiopurines, the level of hypoxanthine-guanine-phosphoribosyl transferase and the rates of the antimetabolite incorporation into RNA and DNA was shown. The sensitivity of tumors to 5-FU correlated with the rates of pyrimidine nucleosides and antimetabolite uptake and the time of retention of labeled 5-FU in RNA. The activites of orotate-phosphoribosyl transferase, uridine kinase, the degree of thymidylate synthetase inhibition of 5-FU and ratio of the de novo to salvage pathways of thymidylate biosynthesis are also important.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002460:Cell Line; D004351:Drug Resistance; D005472:Fluorouracil / Q000494:pharmacology; D007939:Leukemia L1210 / Q000378:metabolism; D015122:Mercaptopurine / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism*; D011685:Purine Nucleotides / Q000096:biosynthesis; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis
D000964:Antimetabolites, Antineoplastic; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D015122:Mercaptopurine; D005472:Fluorouracil