The induction of cytochrome P-450 by isosafrole and related methylenedioxyphenyl compounds

doi:10.1016/S0009-2797(85)80171-X

Chemico-Biological Interactions

Volume 54, 1985, Pages 299-315

https://doi.org/10.1016/S0009-2797(85)80171-X Get rights and content

Summary

Using sucrose gradients, the Ah receptor and a 3-4S binding peak were measured in hepatic cytosol from Dub: ICR, C57BL/6, and DBA/2 male mice. Isosafrole, piperonyl butoxide, and 5--butyl-1,3-benzodioxole were unable to displace 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene from either the Ah receptor or the 3-4S binding peak, in vitro. In in vivo experiments, treatment of C57BL/6 mice with 3-methylcholanthrene caused a 4-fold reduction in Ah receptor binding 2 h after i.p. injection; whereas, isosafrole caused a 2-fold enhancement of the Ah receptor after 24 h. This increase in the Ah receptor binding following isosafrole treatment may be due to induction. 3-Methylcholanthrene treatment of C57BL/6 mice also caused a 3-fold reduction in the 3-4S binding peak 2 h after i.p. injection; isosafrole treatment had little or no effect on the 3-4S peak in C57BL/6 or DBA/2 mice. Both in vivo and in vitro data appear to demonstrate that there is no direct role for the Ah receptor or the 3-4S protein in the regulation of cytochrome P-450 by methylenedioxyphenyl compounds. Using Sephadex G-100 chromatography, a cytosolic protein fraction was obtained from C57BL/6 and Dub: ICR mice which was previously implicated by others as a carrier in the metabolism of benzo[a]pyrene (B[a]P). This fraction was applied to sucrose gradients and sedimented in the 3-4S region. Hence it appears that the 3-4S binding peak may be the carrier described by these workers.

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^*: This work was presented in part at the 1985 Society of Toxicology meeting in San Diego, CA.

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Review articleThe induction of cytochrome P-450 by isosafrole and related methylenedioxyphenyl compounds*

Summary

Life Sci.

Chem-Biol. Interact.

Toxicol. Appl. Pharmacol.

Biochem. Pharmacol.

Toxicol. Lett.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Cell

Biochim. Biophys. Acta

J. Biol. Chem.

J. Biol. Chem.

Isosafrole-induced cytochrome P2-450 in DBA/2N mouse liver. Characterization and genetic control of induction. J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Tetrahedron Lett.

Biochem. Pharmacol.

Review article
The induction of cytochrome P-450 by isosafrole and related methylenedioxyphenyl compounds*

Isosafrole-induced cytochrome P₂-450 in DBA/2N mouse liver. Characterization and genetic control of induction. J. Biol. Chem.