DNA repair synthesis in guineapig pancreas following exposure to nitrosomethylurethane.
NMUT, a known pancreatic carcinogen in guineapigs, alkylates pancreatic DNA and RNA, both in vivo and in vitro. Following the in vivo administration of a single maximum tolerated dose of NMUT (30 mg/kg), a significant increase in 3H-Tdr incorporation into DNA was observed in the duodenal segment of the pancreas after four days; this increase in thymidine incorporation probably represents in vivo DNA repair synthesis. The level of normal DNA synthesis was greater in the duodenal segment than elsewhere in the pancreas. In vitro exposure of pancreatic slices from the duodenal segment to 20 mM NMUT for 30 minutes resulted in a significant increase in 3H-TdR incorporation into DNA in the presence of HU, reflecting DNA repair synthesis following NMUT-induced DNA damage; normal DNA synthesis in the pancreatic slices in vitro was markedly suppressed by 10 mM HU. Studies on the kinetics of DNA repair synthesis in pancreatic slices indicated an initial increase of 3H-TdR incorporation, followed by a steady time-dependent decline. It appears that most of the DNA repair synthesis occurs within two hours after exposure to NMUT.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009605:Nitrosomethylurethane / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014520:Urethane / Q000031:analogs & derivatives*
D002110:Caffeine; D014520:Urethane; D009605:Nitrosomethylurethane; D004247:DNA; D006918:Hydroxyurea