Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene
Aminoazo dyes and other hepatocarcinogenic substances inhibit glucocorticoid-mediated induction of adaptive enzymes, including tyrosine aminotransferase (TAT), in mouse and rat liver. There is a specific relationship between the effect of a carcinogen on TAT induction and its liver carcinogenicity i...
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2015-07-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/356 |
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| author | V. I. Kaledin S. I. Ilnitskaya N. A. Popova O. A. Koval I. A. Pyshnaya L. F. Gulyaeva |
| author_facet | V. I. Kaledin S. I. Ilnitskaya N. A. Popova O. A. Koval I. A. Pyshnaya L. F. Gulyaeva |
| author_sort | V. I. Kaledin |
| collection | DOAJ |
| description | Aminoazo dyes and other hepatocarcinogenic substances inhibit glucocorticoid-mediated induction of adaptive enzymes, including tyrosine aminotransferase (TAT), in mouse and rat liver. There is a specific relationship between the effect of a carcinogen on TAT induction and its liver carcinogenicity in animals. Presuming tumor development being initiated not directly by the chemicals employed but their metabolically activated derivatives, the question arises whether TAT induction is inhibited by carcinogen metabolites or by their parent compounds. The goal of this paper is to shed some light on the issue. Mouse strains differing in the sensitivity to both carcinogenic and antiglucocorticoid (TAT induction inhibitory) effects of the mouse-specific carcinogen ortho- aminoazotoluene (OAT) underwent a set of experimental procedures: ablation of gonadal and adrenal glands, administration of inhibitors (CoCl2, pentachlorophenol), inducers (3,4- benzopyrene, Aroclor 1254, 20-methylcholanthrene) of xenobiotic-metabolizing enzyme activities, and others. The results unequivocally confirm that glucocorticoid induction of TAT activity in mouse liver is inhibited by activated metabolite(s) of OAT rather than by its intact 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 enzyme induction by the carcinogen point to the epigenetic nature of this phenomenon. |
| first_indexed | 2024-03-07T16:07:30Z |
| format | Article |
| id | doaj.art-cb3f9b23b143469da3919982ddfd0520 |
| institution | Directory Open Access Journal |
| issn | 2500-3259 |
| language | English |
| last_indexed | 2024-04-24T11:09:59Z |
| publishDate | 2015-07-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj.art-cb3f9b23b143469da3919982ddfd05202024-04-11T15:30:55ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592015-07-0119113614310.18699/VJ15.017335Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotolueneV. I. Kaledin0S. I. Ilnitskaya1N. A. Popova2O. A. Koval3I. A. Pyshnaya4L. F. Gulyaeva5Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia;Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia;Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia;Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia;Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia;Institute of Molecular Biology and Biophysics SB RAMS, Novosibirsk, RussiaAminoazo dyes and other hepatocarcinogenic substances inhibit glucocorticoid-mediated induction of adaptive enzymes, including tyrosine aminotransferase (TAT), in mouse and rat liver. There is a specific relationship between the effect of a carcinogen on TAT induction and its liver carcinogenicity in animals. Presuming tumor development being initiated not directly by the chemicals employed but their metabolically activated derivatives, the question arises whether TAT induction is inhibited by carcinogen metabolites or by their parent compounds. The goal of this paper is to shed some light on the issue. Mouse strains differing in the sensitivity to both carcinogenic and antiglucocorticoid (TAT induction inhibitory) effects of the mouse-specific carcinogen ortho- aminoazotoluene (OAT) underwent a set of experimental procedures: ablation of gonadal and adrenal glands, administration of inhibitors (CoCl2, pentachlorophenol), inducers (3,4- benzopyrene, Aroclor 1254, 20-methylcholanthrene) of xenobiotic-metabolizing enzyme activities, and others. The results unequivocally confirm that glucocorticoid induction of TAT activity in mouse liver is inhibited by activated metabolite(s) of OAT rather than by its intact 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 enzyme induction by the carcinogen point to the epigenetic nature of this phenomenon.https://vavilov.elpub.ru/jour/article/view/356miceortho-aminoazotoluenetyrosine aminotransferaseenzyme induction and inhibition |
| spellingShingle | V. I. Kaledin S. I. Ilnitskaya N. A. Popova O. A. Koval I. A. Pyshnaya L. F. Gulyaeva Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene Вавиловский журнал генетики и селекции mice ortho-aminoazotoluene tyrosine aminotransferase enzyme induction and inhibition |
| title | Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene |
| title_full | Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene |
| title_fullStr | Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene |
| title_full_unstemmed | Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene |
| title_short | Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene |
| title_sort | induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho aminoazotoluene |
| topic | mice ortho-aminoazotoluene tyrosine aminotransferase enzyme induction and inhibition |
| url | https://vavilov.elpub.ru/jour/article/view/356 |
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