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.
Diliberto
J J
JJ
Experimental Toxicology Division, National Health Effects and Environmental Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. diliberto@herl45.herl.epa.gov
Burgin
D
D
Birnbaum
L S
LS
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology*; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins / Q000378:metabolism*; D004790:Enzyme Induction; D005223:Fats / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011078:Polychlorinated Biphenyls / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins; D005223:Fats; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls; D019388:Cytochrome P-450 CYP1A2; C014024:2,4,5,2',4',5'-hexachlorobiphenyl