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Differences in H-2 recombinant mice in the β-naphthoflavone inducibility of the mixed function monooxygenase, P1-450

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Abstract

The influence of the major histocompatibility complex (H-2 in mouse) on induction of cytochrome P-450-dependent monooxygenase (P1-450) by the prototype polyaromatic hydrocarbon (PAH), β-naphthoflavone, was investigated in C57BL/10 Sn (B10) recombinant congenic mice. The cytosolic Ah-receptor level, as measured by specific binding with [3H]-2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, was significantly lower in B10.A and B10.A (5R) than in either B10, B10.BR, or B10.A(2R), suggesting that the D region of H-2 influences Ah-receptor levels. The responsiveness to β-naphthoflavone, as determined by increased catalytic activity toward benzo(a)pyrene and 7-ethoxycoumarin, was considerably lower in 1310, B10.A, and B10.A(5R) than in B10.BR and somewhat lower than in B10.A(2R) or B10.A(4R) mice. The lower PAH responsiveness in B10.A and B10.A(5R) correlated with their lower Ah-receptor levels while that in B10 appeared to reflect a K-A region influence on PAH responsiveness that was not due to changed Ah-receptor levels. Thus, we conclude that more than one H-2 locus may influence PAH responsiveness, and by different mechanisms.

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References

  • Guengerich, F. P.: Microsomal enzymes involved in toxicity-analysis and separation. In A. W. Hayes (ed.): Hayes Principles and Methods of Toxicology, pp. 612–613, Raven Press, New York, 1982

    Google Scholar 

  • Israel, D. I., Estolano, M. G., Gaeazzi, D. R., and Whitlock, J. P., Jr.: Superinduction of cytochrome P1-450 gene transcription by inhibition of protein synthesis in wild type and variant mouse hepatoma cells. J. Biol. Chem. 260: 5648–5653, 1986

    Google Scholar 

  • Jones, P. B., Galeazzi, D. R., Fisher, J. M., and Whitlock, J. P., Jr.: Control of cytochrome Pl-450 gene expression by dioxin. Science 227: 1499–1502, 1985

    Google Scholar 

  • Koizumi, A., Hasegawa, L., Thomas, I. K., and Imamura, T.: Effect of induction of T-cell-dependent antibody with sheep red blood cells on P-450-dependent and independent xenobiotic metabolizing enzymes. Biochem. Pharmacol. 35: 2743–2748, 1986a

    Google Scholar 

  • Koizumi, A., Hasegawa, L., Walford, R. L., and Imamura, T.: H-2, Ah, and aging: the immune response and inducibility of P-450 mediated monooxygenase activities, xanthine oxidase, and lipid peroxidation in H-2 congenic mice in C57BL/10, C3H, and A strain background. Mech. Ageing Dev. 37: 119–136, 1986b

    Google Scholar 

  • Legraverend, C., Karenlamp, S. O., Biegelow, S. W., Lallwey, C. A., Kozak, C. A., Womack, J. E., and Nebert, D. W.: Aryl hydrocarbon hydroxylase induction by benz(a)anthrathen: Regulatory gene located to the distal portion of mouse chromosome 17. Genetics 107: 447–461, 1984

    Google Scholar 

  • Nebert, D. W. and Gonzalez, F. J.: P-450 genes and evolutionary genetics. Hospital Practice 22: 63–74, 1987

    Google Scholar 

  • Nebert, D. W., Considine, N., and Owens, I. S.: Genetic expression of aryl hydrocarbon hydroxylase induction. VI. Control of monooxygenase activities at or near the same genetic locus. Arch. Biochem. Biophys. 157: 148–159, 1973

    Google Scholar 

  • Okey, A. B., Bondy, G. P., Mason, M. E., Kahl, G. F., Eisen, H. J., Guenthner, T. M., and Nebert, D. W.: Regulatory gene product of the Ah locus. Characterization of the cytosolic inducer-receptor complex and evidence for its nuclear translocation. J. Biol. Chem. 254: 11636–11648, 1979

    Google Scholar 

  • Omura, T. and Sato, R.: The carbon monoxide-binding pigment of the liver microsomes. I. Evidence for hemoprotein nature. J. Biol. Chem. 239: 2370–2378, 1964

    Google Scholar 

  • Robinson, J. R., Considine, N., and Nebert, D. W.: Genetic expression of aryl hydrocarbon hydroxylase induction. J. Biol. Chem. 249: 5851–5859, 1974

    Google Scholar 

  • Whitlock, J. P., Jr.: The regulation of cytochrome P-450 gene expression. Annu. Rev. Pharmacol. Toxicol. 26: 333–369, 1986

    Google Scholar 

  • Yasukochi, Y. and Masters, B. S. S.: Some properties of a detergent solubilized NADPH-cytochrome c (cytochrome P-450) reductase purified by biospecific affinity chromatography. J. Biol. Chem. 251: 5337–5344, 1976

    Google Scholar 

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Koizumi, A., Walford, R.L. & Hasegawa, L. Differences in H-2 recombinant mice in the β-naphthoflavone inducibility of the mixed function monooxygenase, P1-450. Immunogenetics 26, 169–173 (1987). https://doi.org/10.1007/BF00365907

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  • DOI: https://doi.org/10.1007/BF00365907

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