[Biochemical modulation of 5-FU by thymidine and N-phosphoacetyl-L-aspartate: the relation between 5-FU incorporation into RNA and its cytocidal effect].

We attempted to study the relation between 5-FU incorporation into RNA or DNA and the cytocidal effect of 5-FU using thymidine (TdR) and the effect of N-phosphoacetyl-L-aspartate (PALA) on the cytotoxicity of 5-FU. A mouse mammary carcinoma cell line FM3A was used in all of the experiments. The results showed that: addition of TdR to cell cultures resulted in an increase of 5-FU incorporation into RNA and although 5-FU incorporation into nucleic acid decreased, addition of 10(-3) M TdR induced of complete incorporation of 5-FU into only RNA as revealed by alkaline hydrolysis and cesium gradient analysis; no addition of TdR caused 5-FU to be completely incorporated into DNA only; cytocidal effect of 5-FU, in a clonogenic assay, occurred only during the time when TdR was added to the cell culture; PALA possessed the capacity to enhance the cytocidal effect of 5-FU in a clonogenic assay. These results confirmed that 5-FU incorporation into RNA is necessary for the cytocidal effect of 5-FU and that both TdR and PALA are available as 5-FU-modulating agents for enhancement of the cytocidal effect.