Induced Hepatocytes as a Metabolic Activation System for the Mouse-Lymphoma Assay

摘要

The report describes methods developed for the coculture of hepatocytes and mouse lymphoma cells and shows the utility of this system for testing promutagens from several chemical classes. The present study investigated the use of hepatocytes isolated from rats pretreated with a cytochrome P-450 inducer (PB) or a P-448 inducer (BNF). CP-induced mutagenicity was higher in the presence of PB-induced hepatocytes than in control hepatocytes. Control and BNF-induced hepatocytes were evaluated with B(a)P, B(l)A, and BA. A dose-related positive response was observed with B(a)P and B(l)A both in the presence of control or induced hepatocytes; however, somewhat higher mutant frequencies were obtained in the presence of BNF-induced hepatocytes. BA was marginally positive (approximately 2 x b.g.) in the presence of control hepatocytes and weakly positive in the presence of BNF-induced hepatocytes. Benzene was evaluated using control and both PB and BNF-induced hepatocytes. Slight dose-related increases in the mutant frequency were observed. These increases were not sufficiently high to meet criteria for a positive response. The response was not affected by using induced rather than control hepatocytes. (Copyright (c) 1989 Elsevier Science Publishers B.V. (Biomedical Division).)