METABOLISM OF 5-FLUOROURACIL IN SENSITIVE AND RESISTANT TUMOR-CELLS

Abstract

Thymidine kinase, dTMP kinase and DNA polymerase activities were determined in cell lines of rat ascites of AH [AH44, AH109A] hepatoma, mouse L1210 leukemia and rat Yoshida sarcoma that were sensitive and resistant to 5-fluorouracil (5-FU). The levels of these enzymes in tumor cells were not consistently related to the sensitivity to 5-FU. A marked difference was observed between sensitive and resistant cell lines of L1210 leukemia and Yoshida sarcoma in the uptake of labeled 5-FU into the acid-soluble, nucleotide and RNA fractions, the rate of incorporation of 5-FU into these fractions being 3-5 times greater in sensitive tumor cells than in resistant tumor cells. The radioactivities in the acid-soluble fractions of AH44 (sensitive) and AH109A (resistant) were similar after incubation of these cells with labeled 5-FU in vitro. A smaller volume of ascites and lower cell number were observed in AH44 (sensitive)-bearing rats than AH109A (resistant)-bearing rats. The 5-FU injected i.p. may have been diluted by ascites more in AH109A (resistant)-bearing rats than in AH44 (sensitive)-bearing rats.