The Ah locus: correlation of intranuclear appearance of inducer-receptor complex with induction of cytochrome P1-450 mRNA

Abstract

The Ah locus regulates the induction of cytochrome P1-450 by foreign chemicals such as 3-methyl-cholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. The induction process is controlled by the cytosolic Ah receptor. The cytosolic and nuclear Ah receptors were studied in the liver from inbred C57BL/6N (Ahb/Ahb) mice, inbred DBA/2N (Ahd/Ahd) mice and heterozygotes (Ahb/Ahd) and homozygotes (Ahd/Ahd) derived from the (C57BL/6N X DBA/2N)F1 X DBA/2N backcross. After [3H-1,6]-2,3,7,8-tetrachlorodibenzo-p-dioxin (3H-TCDD) is given in vivo, the receptor in Ahb/Anb and Ahb/Ahd mice is detectable in the cytoplasm and nucleus; in Ahd/Ahd mice the receptor is not measurable in the cytosol, but is found in the nucleus at levels one fourth to one fifth of those in Ahb/Ahb mice. P1-450 (23S) mRNA content was estimated by Northern hybridization and by Rot analysis with a mouse P1-450 cloned cDNA. An excellent dose-response relationship (r = 0.99) was found between the amount of 3H-TCDD-Ah receptor complex appearing in the nucleus and the quantity of P1-450 mRNA induced in mice with all three possible Ah genotypes.