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.
Proskuryakov
S Ya
SY
Medical Radiological Research Center, Russian Academy of Medical Sciences, Obninsk, Russia.
Konoplyannikov
A G
AG
Konoplyannikova
O A
OA
Ulyanova
L P
LP
Tsyb
A F
AF
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D002273:Carcinogens / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005720:Gamma Rays; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D019813:1,2-Dimethylhydrazine; D007213:Indomethacin