Chronobiology of the mammalian response to ionizing radiation. Potential applications in oncology.

Ionizing radiation from all sources under appropriate conditions leads to cell death and tissue damage. It is used in cancer treatment under the assumption of a higher radiosensitivity of the fast dividing tumor cells as compared with adjacent host tissues. The radiosensitivities of proliferating host tissues like bone marrow and gastrointestinal lining epithelium are dose limiting. Since these host tissues and many tumors show circadian and other periodicities in their cell proliferation, the timing of radiation treatment according to host and/or tumor rhythms is expected to improve the toxic/therapeutic ratio of the treatment. The experimental data on the chronobiology of radiation exposure show circadian rhythmicity in radiation response after whole body irradiation in mice and rats with highest toxicity in light-dark 12h:12h synchronized animals during their daily activity span. Bone marrow toxicity as well as gastrointestinal epithelial damage show circadian rhythms in part due to radiation damage to the stem cells involved and especially in the intestine also due to damage to the microvasculature. Chronoradiotherapy of malignant tumors seems promising, alone or in combination with response modifiers, provided the host and potential tumor rhythms can be monitored.