Genetically mediated induction of aryl hydrocarbon hydroxylase activity in mice by polychlorinated dibenzofuran isomers and 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Hepatic aryl hydrocarbon hydroxylase (AHH)-inducing potency of toxic polychlorinated aromatic hydrocarbons such as polychlorinated dibenzofurans (PCDFs), 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in four inbred strains of mice with different phenotypes of Ah locus, i.e., AHH-responsive strains: C57BL/6N and AKR/Ms Qdj, and AHH-nonresponsive strains: DBA/2Cr Slc and Qdj; DDD. Eight individual PCDF isomers or TCDD were administered IP in doses of 30 micrograms/kg; HCB was given in a dose of 120 micrograms/kg. In AHH-nonresponsive strains of mice, only TCDD significantly induced hepatic AHH activity, while in AHH-responsive strains, 2,3,7,8-tetrachlorodibenzofuran(2,3,7,8-TCDF), 1,2,3,7,8-pentachlorodibenzofuran(1,2,3,7,8-PCDF), 2,3,4,7,8-pentachlorodibenzofuran(2,3,4,7,8-PCDF), and TCDD significantly enhanced the enzyme activity, and the induced AHH activities with the three PCDF isomers were about 30-65% of those of TCDD. These results indicate that AHH responsiveness in mice segregates with the induction of AHH activity by PCDF isomers and may also segregate with the toxic potency of the isomers; i.e., toxic potencies of 2,3,7,8-TCDF, 1,2,3,7,8-PCDF, and 2,3,4,7,8-PCDF in AHH-responsive strains of mice may be much greater than those in AHH-nonresponsive strains of mice. Taking into account both the potent AHH inducibility and the high bioaccumulation of 2,3,7,8-TCDF, 1,2,3,7,8-PCDF, and 2,3,4,7,8-PCDF, these three PCDF isomers should be given greater attention with regard to environmental contamination.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001572:Benzofurans / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011108:Polymers; D013045:Species Specificity
D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; C016068:polychlorodibenzofuran; D008748:Methylcholanthrene; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; C027309:3,4,5,3',4',5'-hexachlorobiphenyl