Effects of 5-fluorouracil on human colon carcinoma and solid rat Walker 256 carcinosarcoma: evaluation as in vitro predictors of clinical response.
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| Abstract |
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.
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| Authors | P Klubes, I Cerna, K Connelly, G W Geelhoed, H G Mandel |
| Journal | Cancer treatment reports (Cancer Treat Rep) Vol. 62 Issue 7 Pg. 1065-73 (Jul 1978) ISSN: 0361-5960 [Print] United States |
| PMID | 688247 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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