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.