Studies of DNA damage in rat pancreas and liver by 6-diazo-5-oxo-L-norleucine, ethyl diazoacetate and azaserine.
One hour following intraperitoneal injection of the pancreatic and liver carcinogen azaserine, 10 mg/kg (0.06 mmol/kg), DNA damage is present in both pancreas and liver of Wistar/Lewis rats as determined with alkaline sucrose gradients. Single injections (0.06 mmol/kg) of either of 2 structural analogues of azaserine, 6-diazo-5-oxo-L-norleucine (DON) and ethyl diazoacetate (EDA), do not damage pancreatic or liver DNA. EDA administered at 0.5 mmol/kg damages liver DNA, but not pancreatic DNA. Total radioactivity in pancreas and liver of Wistar rats 1 h after intravenous injection of [14C]azaserine, (10 microCi/kg), is 2.8 and 1.3 times respectively, the level of 14C-activity in pancreas and liver following injection [14C]EDA. Three to four times as much [14C]EDA localizes in the liver of Wistar rats as in the pancreas. Azaserine (0.06 mmol/kg weekly for 6 weeks) induces atypical acinar cell nodules (AACN) in pancreas of Wistar/Lewis rats. DON (0.06 mmol/kg weekly for 6 weeks) induces an elevated incidence, but low number of AACN in pancreas. EDA (0.10 mmol/kg weekly for 6 weeks) does not induce pancreatic AACN.
D000818:Animals; D001377:Azaserine / Q000378:metabolism / Q000633:toxicity*; D001391:Azo Compounds / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA; D003979:Diazonium Compounds / Q000633:toxicity*; D003980:Diazooxonorleucine / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains
D001391:Azo Compounds; D002273:Carcinogens; D003979:Diazonium Compounds; D003980:Diazooxonorleucine; D001377:Azaserine; D004247:DNA; C032111:diazoacetic ester