title: 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 AH hepatoma, L1210 leukemia, and Yoshida sarcoma that were sensitive and resistant to 5-fluorouracil (5-FU). It was found that the levels of these enzymes in tumor cells were not consistently related to the property of 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 to 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. However, a smaller volume of ascites and lower cell number were observed in AH44 (sensitive)-bearing rats than in AH109A (resistant)-bearing rats. These in vivo results indicate that the 5-FU injected intraperitoneally was diluted by ascites more in AH109A (resistant)-bearing rats than in AH44 (sensitive)-bearing rats.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D012334:RNA, Neoplasm / Q000378:metabolism; D051381:Rats; D012517:Sarcoma, Yoshida / Q000378:metabolism*; D013937:Thymidine Kinase / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D005472:Fluorouracil