Selective induction of murine liver cytochrome p450 IIB1 by Halogenated hydrocarbons

Abstract

Thirteen halogenated hydrocarbons, 1,1,1,2‐tetrachloroethane (1,1,1,2‐TCE), 1,1,2,2‐tetrachloroethane (1,1,2,2‐TCE), pentachloroethane (PCE), 1,2‐dibromoethane (DBE), 1,1,2,2‐tetrabromoethane (1,1,2,2‐TBE), iodoethane (IE), 1,1‐dichloroethane (1,1‐DCE), 1,1,1‐trichloroethane (1,1,1‐TCE), 1,1,2‐trichloro‐ethane (1,1,2‐TCE), dichloromethane (DCM), 1,1‐dichloroethylene (1,1‐DCEE) and trans 1,2‐dichloro‐ethylene (t1,2‐DCE) were evaluated for their ability to modulate specific cytochrome P450 (cyt P450) isoforms following in vivo administration in male mice. Each chemical was administered (i.p.) in equivalent doses (50, 25, 12.5 and 6.25% of the respective LD50). Total cyt P450 and selected microsomal monoxygenase activities towards different P450 isoenzymes (classes IA1, UBI, IIE1 and IIIA P450) were examined in hepatic microsomes. With the exception of 1,1‐DCE, all considered hydrocarbons were inducers of Cyp2B1 genes, as exemplified by the enhancement of pentoxyresorufin O‐dealkylation. A 1.5‐(DBE, DCM) to ...