Role of cyclooxygenases in the stimulatory effect of carcinogen 1,2-dimethylhydrazine on stem cell survival in the intestinal epithelium and bone marrow.

In vivo experimental studies showed that 1,2-dimethylhydrazine and product of its metabolism in the body azoximethane improve postradiation survival of two types of stem cells in the adult organism: hemopoietic stem cells and intestinal epithelial stem cells. This effect similar to the well-known radioprotective effect of E. coli lipopolysaccharide was observed, when the carcinogen was administered 1 day before gamma-irradiation. Treatment with 1,2-dimethylhydrazine prolonged the mean life-span of mice irradiated in supralethal doses inducing death of the majority of intestinal epithelial stem cells. Nonspecific cyclooxygenase inhibitor indometacin weakened this radioprotective effect of 1,2-dimethylhydrazine. We also found that carcinogen 1,2-dimethylhydrazine improved survival of hemopoietic stem cells. However, in contrast to intestinal epithelial stem cells, indometacin did not inhibit the radioprotective effect of the carcinogen. The radioprotective effect of 1,2-dimethylhydrazine and lipopolysaccharide on stem cells in the presence of indometacin was a sum of individual effects of these preparations and indometacin.