Although disruption of the circadian rhythm had been traditionally considered as a pathological sign, there is an increasing recognition that an existence of internal disorder (or chaos) in the organism's homeostasis is, to some degree, essential to the organism's well being. In this study we explored the effects of rhythm scrambling by exposure to random light/dark (RLD) alternation or by hydrocortisone administration. The variables measured were the toxicity of Adriamycin, Vincristin, Cisplatinum and Cyclophosphamide in C57Bl/6J mice and the survival of EL4 lymphoma-bearing mice, before and after chemotherapy. Rhythm alterations were determined by WBC counts and plasma Alkaline Phosphatase activity. Injections of Adriamycin, Cisplatinum and Vincristin in RLD conditions resulted in a better survival than in control groups of mice kept in LD illumination regimen, although the differences between the groups were significant only for injection of Adriamycin. RLD conditions imposed a "protective" effect on survival of tumor-bearing mice. On the 94th day, 20% of the injected mice in RLD conditions still survived while, there were no survivors beyond 38 days in control group. Chemotherapy had a more prominent beneficial effect on survival in RLD group, as compared to LD group. The injections of hydrocortisone had detrimental effect on survival in both illumination schedules. However, the survival in the RLD group was still better than in the LD group. These experiments indicate that temporal disorganization has beneficial effects on lymphoma-bearing mice and could be used for development of new therapeutic modalities.
- Drug efficacy
- Drug toxicity
- Rhythm disorganization
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)
- Pharmacology, Toxicology and Pharmaceutics (all)