Effects of 5-fluorouracil on human colon carcinoma and solid rat Walker 256 carcinosarcoma: evaluation as in vitro predictors of clinical response.
Several biochemical effects of 5-fluorouracil (5-FU) including inhibition of the incorporation of 3H-deoxyuridine (3H-UdR) into DNA, inhibition of ribosome formation, and formation of 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) were examined in samples of human colon carcinomas to determine if any of these drug effects might have predictive value as a reliable guide to 5-FU therapy. For comparison, the solid rat Walker 256 carcinosarcoma, which is only minimally responsive to 5-FU, was also studied. For each of the biochemical effects of 5-FU measured in the various samples of Walker 256 tumors, the responses were consistent and varied within a narrow range. In contrast, the formation of FdUMP from 5-FU and the degree of inhibition of the incorporation of 3H-UdR into DNA by 5-FU were extremely variable in the population of human colon carcinomas examined. In all human tumors examined, 5-FU caused a reduction in the formation of ribosomes, but even in the absence of 5-FU, the total amount of ribosome synthesis was so low that it makes measurement difficult to quantitate. Based on our data, a study might be warranted to determine if there is a correlation between FdUMP formation and responsiveness of colon carcinoma to 5-FU therapy.
D000818:Animals; D002279:Carcinoma 256, Walker / Q000188:drug therapy / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003857:Deoxyuridine / Q000378:metabolism; D005468:Fluorodeoxyuridylate / Q000096:biosynthesis; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D012270:Ribosomes / Q000187:drug effects*
D004273:DNA, Neoplasm; D005468:Fluorodeoxyuridylate; D005472:Fluorouracil; D003857:Deoxyuridine