Role of CYP1A2 in hepatic sequestration of dioxin: studies using CYP1A2 knock-out mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin), most potent of the polyhalogenated aromatic hydrocarbons, has been studied in a variety of genetically normal species. Transgenic mice lacking a cytochrome P450 1A2 gene were used to study the influence of the CYP1A2 gene on the hepatic sequestration and distribution of TCDD, 4-PeCDF (2,3,4,7,8-pentachlorodibenzofuran; dioxin-like compound), and PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl; non-dioxin-like PCB (polychlorinated biphenyl)). The knock-out mice were compared to their age-matched lineage strains of C57BL/6N (1A2+/+; Ah(b)) and 129/Sv (1A2+/+; Ah(d)) for each compound. As demonstrated by the liver-to-adipose tissue (L/F) concentration ratios, there was no hepatic sequestering of TCDD and 4-PeCDF in the transgenic knock-out mice.