Sparing effect of cyclophosphamide (NSC-26271) pretreatment on animals lethally treated with gamma-irradiation.

Cyclophosphamide (CP) can protect mice from gamma-irradiation-induced lethality, the timing of the dose of CP in relation to the irradiation being the critical factor. The most sparing effect is achieved when CP is injected 3 days before irradiation. The protection is mediated by enhanced hemopoietic recovery seen in animals given the most favorable combination ofCP and gamma-irradiation. This rapid recovery cannot be explained by the reduced sensitivity of hemopoietic stem cells after CP treatment to subsequent irradiation although survival of a few radioresistant stem cells cannot be ruled out. Stimulus to repopulate by nonspecific depletion of the bone marrow is not the explanation either, since CP itself appears to play an important role in this effect. The role of the spleen is not critical in this phenomenon and attempts have failed to demonstrate the presence of a humoral factor which can restore bone marrow depleted by gamma-irradiation in the serum of animals treated with CP. CP given 3 days before irradiation appears to result in a purely additive effect against malignant tissue in mice, providing a useful differential kill on tumor tissue at the same time that it provides the maximum protection of normal tissue.