Species Specific Hepatocarcinogen Inhibition of the Glucocorticoid Induction of Tyrosine Aminotransferase Gene in Mouse and Rat Liver

T. I. Merkulova^1*, K. Y. Kropachev¹, O. A. Timofeeva², G. V. Vasiliev¹, S. I. Ilnitskaya¹, Z. B. Levashova¹, V. F. Kobzev¹, and V. I. Kaledin¹

¹Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, pr. Lavrentieva 10, Novosibirsk 630090, Russia; fax: (3832) 33-1278; E-mail: merkti@niboch.nsc.ru

²Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences, pr. Lavrentieva 8, Novosibirsk 630090, Russia; fax: (3832) 33-3677; E-mail: oa.tim@niboch.nsc.ru

^* To whom correspondence should be addressed.

Received March 16, 2002; Revision received May 14, 2002

---

3´-Methyl-4-dimethylaminoazobenzene (3´-MeDAB) is a potent hepatocarcinogen in rats and a weak carcinogen in mice, whereas o-aminoazotoluene (OAT) is a potent hepatocarcinogen in mice but weak hepatocarcinogen in rats. They significantly suppress glucocorticoid induction of tyrosine aminotransferase (TAT) in the liver of sensitive animals and have minor effect on the induction of this enzyme in the liver of resistant animals (3´-MeDAB-treated mice and OAT-treated rats). The inhibitory effect of these carcinogens is realized at the level of gene transcription (decreased accumulation of TAT mRNA). This effect is mediated via reduction of DNA-binding activity of transcription factor HNF3 (without decrease of its content) without any involvement of the glucocorticoid receptor. It was shown that carcinogens influence DNA-binding activity of HNF3 via an unknown nuclear factor.

---

KEY WORDS: hepatocarcinogens, tyrosine aminotransferase, glucocorticoid induction, glucocorticoid receptor, transcription factor HNF3

---