Biochemical studies of six nitrogen-containing heterocycles in rat tissues.
Female rats were dosed orally with one-fifth the LD50 of either 1-nitrosopiperidine (a carcinogen), cyclohexylamine, piperidine, 4-carboxy-1-nitrosopiperidine, 4-cyclohexyl-1-nitrosopiperidine or 2,6-dimethyl-1-nitrosopiperidine at 21 and 4 hr before they were killed. The five noncarcinogenic compounds had no effects on any experimental variables examined [hepatic DNA damage, ornithine decarboxylase (ODC) activity, serum alanine aminotransferase (SGPT) activity, cytochrome P-450 and glutathione content]. After administration of 40 mg/kg of 1-nitrosopiperidine, marked hepatic DNA damage and a 3- to 7-fold increase in the activity of hepatic ODC were observed. 1-Nitrosopiperidine (120 mg/kg, 3/5 LD50) caused DNA damage in rat liver and esophagus but not in leukocytes. This higher dose of 1-nitrosopiperidine also increased hepatic ornithine decarboxylase activity by 9-fold. Thus, this hepatic biochemical assay system correctly identified the one carcinogen and the five noncarcinogens in this series of six nitrogen-containing heterocycles.
Kitchin
K T
KT
Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Brown
J L
JL
Lijinsky
W
W
D000818:Animals; D001769:Blood / Q000187:drug effects* / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009584:Nitrogen; D009602:Nitrosamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D006571:Heterocyclic Compounds; D009602:Nitrosamines; C002743:N-nitrosopiperidine; D009584:Nitrogen