Cytotoxicity and mode of action of aliphatic dicarboxylic acids in L1210 lymphocytic leukemia cells

The aliphatic dicarboxylic acid surprisingly afforded potent cytotoxicity a nd in vivo antineoplastic activity. The agents were active against the grow th of a variety of leukemias, lymphomas, and suspended HeLa uterine carcino ma. Suppression of growth of cell lines derived from human solid cancers, e .g. SW-480 colon adenocarcinoma, lung MB- 9812, glioma HS-683, and rat oste osarcoma UMR-106 was observed. A mode of action study in L1210 lymphoid leu kemia demonstrated that DNA and RNA syntheses were inhibited at multiple si tes including ribonucleoside reductase, purine de novo synthesis at PRPP-am idotransferase and IMP dehydrogenase and nucleic acid kinases. These studie s could not exclude the possibility that the agents also interacted with th e DNA molecule itself interfering with the utilization of the template.