Modification of tumor and normal tissue radioresponse in mice by N-methylformamide

The effects of the differentiation-inducing agent N-methylformamide (NMF) on the in vivo response of the murine tumor FSA and its pulmonary metastases to ionizing radiation were investigated. In addition, the radioresponse of acutely responding normal tissues was determined in mice receiving systemic NMF. A dosage of 300 mg/kg administered for 8 days had little effect on the FSA tumor growth, yet enhanced the growth inhibitory actions of ionizing radiation with dose enhancement factors ranging from 1.5 to 1.7. Administration of NMF also enhanced the radiation response of FSA micrometastases. The response to irradiation of hematopoietic tissue, jejunum, and testes in mice receiving NMF was also investigated. NMF administered before or before and after radiation enhanced the formation of endogenous spleen colonies, yet did not influence the LD50/30 for radiation. Jejunal crypt cell survival after radiation was slightly increased in mice receiving NMF, but the survival of spermatogonia after radiation was not affected. These data indicate that NMF administration results in an increase in the radiosensitivity of the FSA tumor and its metastases with no concomitant increase in the radiation response of the normal tissue tested. Thus, at least in this model system, a therapeutic gain is achieved through the combination of NMF and ionizing radiation.