Combinations of 5-FU, hypoxanthine and allopurinol in chemotherapy for human colon adenocarcinoma xenografts.
A series of four human colon adenocarcinomas, growing as xenografts in immune-deprived mice, have been used to evaluate the efficacy of 5-FU in combination with two purines, hypoxanthine (Hx) and allopurinol (HPP), which have reduced the toxicity of 5-FU in host mice. Tumor-bearing mice were treated at 7-day intervals with 5-FU administered simultaneously with the protecting agents (Hx and HPP). Two tumor lines (HxVRC5 and HxGC3), insensitive to 5-FU alone, failed to show any response to this combination. In 5-FU-sensitive HxELC2 tumors, the combination of 5-FU with Hx and HPP did not increase the therapeutic index, and in HxHC1 xenografts, antagonism to 5-FU cytotoxicity was observed. Tumor response in relation to the pathways of 5-FU metabolism is discussed.
D000230:Adenocarcinoma / Q000188:drug therapy*; D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D007042:Hypoxanthines; D019271:Hypoxanthine; D000493:Allopurinol; D005472:Fluorouracil