In Vitro Generation of a Chemically Reactive Metabolite of 2,5,2′,5′-Tetrachlorobiphenyl by Rhesus Monkey Liver Microsomes

Abstract

Summary

Incubation of tritiated 2,5,-2′,5′-tetrachlorobiphenyl with normal monkey liver microsomes in a NADPH-generating system results in the formation of active metabolite(s) of the [³H]2,5,2′,5′-tetrachlorobiphenyl capable of covalently binding to RNA and protein isolated from the incubation mixture. The metabolite is not formed when the control microsomes are held at 100° for 10 min prior to incubation. The addition of microsomal supernate to the solution causes an increase in the binding of the active metabolite to macromolecules while the addition of glutathione to the incubation medium significantly inhibits this increase.

This investigation was supported in part by U.S. Public Health Service Grants ES-00472, ES-00958, and RR-00167 from the National Institutes of Health. This is Primate Center Publication No. 15-019.