ALTERATIONS OF CIRCADIAN-RHYTHMS IN MICE INDUCED BY ANTICANCER DRUGS

Carboplatinum was injected into four groups of mice for 5 successive d ays at one out of four daily equidistant hours. Upon the cessation of these injections. granulocyte colony stimulating Factor was injected i nto half of these mice for 2 days at the same times. The stimulating f actor was also injected into groups of untreated mice for 2 days at th e same times. In each experiment the rhythms of four variables were mo nitored after the cessation of all injections: peripheral WBC count, b one marrow and sperm stem cells DNA synthesis, and sperm ribosomal RNA content. The results indicated that in the course of repeated drug ad ministrations, variables' rhythm parameters (phases and periods, were altered. These changes have to be considered in chronotherapeutic sche dules when variables which serve for toxicity diagnosis or as drug tar get are rhythmic in nature.