Cytokines such as IL 1 and TNF radioprotect mice from lethal hematopoietic failure if given prior to irradiation. Factors contributing to radioprotection include cytokine induction of other hematopoietic cytokines, receptors for such cytokines and MnSOD, an oxygen radical scavenger. We have also identified another hematopoietic cytokine, stem cell factor (SCF) as radioprotective. Although SCF and IL 1 do not induce one another, IL 1 upregulates the expression of receptors for SCF (c-kit proto-oncogene) on bone marrow cells, which may account for the synergistic radioprotective effects of IL I and SCF. Since radioprotection may also involve DNA repair processes, we have postulated that cytokine may modulate DNA repair processes. Drs. Turetskaya and Nedospasov have therefore cloned the murine GADD45 gene to provide a means of testing this hypothesis. This gene is induced by DNA damage and apparently controlled by p53. We have detected the expression of GADD45 mRNA in murine liver and thymus. We are now in a position to further evaluate the effects of irradiation and cytokines on this gene and other genes that may be induced by irradiation damage such as MDM-2 and WAF-1.
