Induction by 5-fluorouracil of a major phase difference in the circadian profiles of DNA synthesis between the Ehrlich ascites carcinoma and five normal organs.
DNA synthetic activity (DNA-SA) was measured by the incorporation of tritiated thymidine (TDR) into chemically isolated DNA. DNA-SA was monitored every 3 h over a 60-h period in the Ehrlich ascites carcinoma (EAC), tongue, bone marrow, ileum, stomach and rectum in mice which had received 50 mg/kg 5-fluorouracil (FU) at 17:00 h. FU was given in an attempt to induce major phase differences in the circadian profiles of DNA-SA between the EAC and the normal organs. Subsequent to the FU treatment, a time period 15 h in duration, was identified when DNA-SA in the EAC was at or near a maximal level (125-190 cpm/micrograms DNA) whereas DNA-SA in all 5 normal organs was at or near a minimal level (less than 60 cpm/micrograms DNA). Induction of such quantitative (actual levels of DNA-SA) and qualitative (180 degrees circadian phase change) differences between the normal and neoplastic cells in the same host should be useful in designing a more effective chemotherapeutic protocol for this tumor-host situation.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D005472:Fluorouracil / Q000494:pharmacology*; D007082:Ileum / Q000378:metabolism; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D012588:Scintillation Counting; D014059:Tongue / Q000378:metabolism
D004247:DNA; D005472:Fluorouracil