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.