[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.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000378:metabolism*; D013936:Thymidine / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D004273:DNA, Neoplasm; D009943:Organophosphorus Compounds; D012334:RNA, Neoplasm; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil; D013936:Thymidine