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INDUCED HEPATOCYTES AS A METABOLIC ACTIVATION SYSTEM FOR THE MOUSE-LYMPHOMA ASSAY
Citation:
Oglesby, L., K. Brock, AND M. Moore. INDUCED HEPATOCYTES AS A METABOLIC ACTIVATION SYSTEM FOR THE MOUSE-LYMPHOMA ASSAY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/233 (NTIS PB90145970).
Description:
We have developed methods for the coculture of hepatocytes and mouse lymphoma cells and have shown the utility of this system for testing promutagens from several chemical classes (Brock et al., 1987). In the present study we investigated the use of hepatocytes isolated from rats pretreated with a cytochrome P-450 inducer (PB) or a P-448 inducer (BNF). P-induced mutagenicity was higher in the presence of PB-induced hepatocytes than in control hepatocytes. ontrol and BNF-induced hepatocytes were evaluated with B(a)P, B(l)A, and BA. ose-related positive response was observed with B(a)P and B(1)A both in the presence of control or induced hepatocytes; however, somewhat higher mutant frequencies were obtained in the presence of BNF-induced hepatocytes. A 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 PBand BNF-induced hepatocytes. light dose-related increases in the mutant frequency were observed. hese increases were not sufficiently high to meet our criteria for a positive response. he response was not affected by using induced rather than control hepatocytes. hese studies indicate that for some chemicals the mutaaenic response can he increased by inducing hepatocytes prior to isolation and cocultivation.
