Effect of cyclophosphamide on circadian rhythms in mitosis and DNA synthesis in normal mice and mice bearing the Ehrlich ascites carcinoma.

A single dose of 50 mg/kg of cyclophosphamide (cytoxan or CTX) was given to non-tumor-bearing mice and to mice bearing the Ehrlich ascites carcinoma (EAC). Circadian profiles in mitotic index and/or DNA-synthetic activity (DNA-SA: incorporation of tritiated thymidine into chemically isolated DNA) were monitored in normal organs and in the EAC. Mice were standardized to and kept on a 12 h: 12 h light-dark cycle with light from 06.00 to 18.00 h (CST or central standard time). In non-tumor-bearing mice, CTX at 05.00 h was more disruptive of the normal circadian profiles than was CTX at 17.00 h. CTX at 17.00 h was selected as the treatment to attempt to induce changes in DNA-SA of the EAC but concomitantly preserve the normal phasing of the circadian rhythms in the normal organs. Except for the bone marrow, CTX at 17.00 h did not perturb the normal circadian patterns in the normal organs (cornea, tongue, spleen, liver, ileum, rectum) of the EAC-bearing mice. CTX did cause a significant and prolonged inhibition of DNA-SA in the EAC. However, CTX-treated, EAC-bearing mice did not live significantly longer than saline-treated EAC-bearing mice.