The effect of 4-(4-chlorobenzyl)pyridine (4-CBP) on rat hepatic microsomal cytochrome P450 (P450) and its molecular species (CYP2B1, 2E1, 3A2, 2C11, and 2C12), and on drug-metabolizing enzyme activities were examined in vivo and in vitro. Treatment of rats with 4-CBP resulted in the induction of P450 and drug-metabolizing enzymes in a dose-dependent manner, but it was markedly inhibitory at hig...

A 9-week in vivo rasH2/butylhydroxytoluene (BHT) model for the detection of genotoxic lung carcinogens was validated, using six potent positive test compounds, dimethylnitrosamine (DMN; 15 mg/kg, i.p.), diethylnitrosamine (DEN; 100 mg/kg, i.p.), ethylnitrosourea (ENU; 120 mg/kg, i.p.), 3-methylcholanthrene (MC; 100 mg/kg, i.p.), 7,12-dimethylbenz(a)anthracene (DMBA; 5 mg/kg, i.g.) and benzo(a)p...

The host-mediated assay was initially conceived as a system for determining the mutagenic potential of mammalian metabolites of foreign compounds for bacteria (1). In practice, a genetically defined indicator microorganism is injected into the peritoneal cavity of mice which are then administered the substance under test, either orally or parenterally. After a specified time -usually 3 hr-the m...

BACKGROUND A metabolomic study of biomarkers associated with dimethylnitrosamine (DMN)-induced hepatic fibrosis in Sprague-Dawley rats was performed using GC-MS. The clinical chemistry of the collected blood and the histopathology of excised liver samples were examined, and urine samples were prepared by solvent extraction. RESULTS Through pattern analysis, the DMN-treated group was divided i...

The toxic and carcinogenic actions of four methylnitrosamine or -amide compounds, given as a single intraperitoneal injection to newborn and adult inbred Swiss mice, were examined. Toxicity was approximately directly proportional to the stability of the three compounds capable of methylating macromolecules in vitro. Methylnitrosourea induced a high incidence of thymic lymphomas in adults and ne...

Treatment of rats with low doses of hepatocarcinogens is associated with a number of phenomena, including nuclear enlargement and altered nucleocytoplasmic compartmentation, which potentially reflect initiatory changes. Since a number of investigations have indicated that changes in ploidy may relate to the development of altered foci and/or hepatocellular carcinomas in liver, and since nuclear...

Hench (1933) described the ameliorating effect of hepatic disease on rheumatoid arthritis. Although jaundice was thought to be the determining factor in these remissions, it was not possible to reproduce the phenomenon by administration of bilirubin and bile salts (Hench, 1940), and a satisfactory explanation of its mechanism has never been offered (Hill and Holley, 1966). This was investigated...