Evaluation of cytotoxic agents in human colonic tumor xenografts and mouse gastrointestinal tissues using a ³H-thymidine fractional incorporation assay

Drug induced changes in ³H-thymidine fractional incorporation (TFI) in 4 human colonic xenograft lines and mouse gastrointestinal tissues have been related to the growth inhibition and host toxicity respectively. Using the TFI assay, the combinations of actinomycin D with cyclophosphamide and methyl CCNU with pentamethyl-melamine have been examined. Both combinations showed greater than additive activity against only 1 of the 3 xenograft lines in which they were tested. The TFI assay allows more rapid evaluation of drug activity and is more sensitive than growth delay studies. It also allows quantitative measurement of cytotoxic activity in gastrointestinal tissues after sublethal dose levels.