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Induction of tyrosine aminotransferase in mice is inhibited by the activated metabolites of ortho-aminoazotoluene

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Russian Journal of Genetics: Applied Research

Abstract

Aminoazo dyes and other hepatocarcinogenic substances inhibit glucocorticoid-mediated induction of adaptive enzymes, including tyrosine aminotransferase (TAT), in the liver of mice and rats. There is a specific relationship between the effect of a carcinogen on TAT induction and its liver carcinogenicity in animals. If the presumption that tumors are caused not by the chemicals employed but their metabolically activated derivatives is correct, the question arises whether TAT induction is inhibited by carcinogen metabolites or the initial compounds. The goal of this paper is to shed some light on the issue. Mice strains differing in sensitivity to both the carcinogenic and antiglucocorticoid (inhibits TAT induction) effects of the mouse-specific carcinogen ortho-aminoazotoluene (OAT) underwent a set of experimental procedures: ablation of sex and adrenal glands, administration of inhibitors (CoCl2 and pentachlorophenol) or inducers (3,4-benzopyrene, Aroclor 1254, and 20-methylcholanthrene) of xenobiotic-metabolizing enzyme activities, etc. The results unequivocally confirm that glucocorticoid induction of TAT activity in the mouse liver is inhibited by the activated OAT metabolite(s) rather than its initial molecules. In contrast, nonspecific genotoxic agents such as cyclophosphamide and cisplatin exert no effect on TAT induction by glucocorticoids. The wide occurrence (practically in each TAT-expressing hepatocyte) and rapidly reversible inhibition of the enzyme induction by the carcinogen point to the epigenetic nature of this phenomenon.

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    V. I. Kaledin, S. I. Ilnitskaya & N. A. Popova

  2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    O. A. Koval & I. A. Pyshnaya

  3. Institute of Molecular Biology and Biophysics, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk, 630060, Russia

    L. F. Gulyaeva

Authors
  1. V. I. Kaledin
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  2. S. I. Ilnitskaya
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  3. N. A. Popova
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  4. O. A. Koval
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  5. I. A. Pyshnaya
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  6. L. F. Gulyaeva
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Correspondence to V. I. Kaledin.

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Original Russian Text © V.I. Kaledin, S.I. Ilnitskaya, N.A. Popova, O.A. Koval, I.A. Pyshnaya, L.F. Gulyaeva, 2015, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2015, Vol. 19, No. 1, pp. 136–143.

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Kaledin, V.I., Ilnitskaya, S.I., Popova, N.A. et al. Induction of tyrosine aminotransferase in mice is inhibited by the activated metabolites of ortho-aminoazotoluene. Russ J Genet Appl Res 6, 91–98 (2016). https://doi.org/10.1134/S207905971601007X

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  • DOI: https://doi.org/10.1134/S207905971601007X

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