Species specific hepatocarcinogen inhibition of the glucocorticoid induction of tyrosine aminotransferase gene in mouse and rat liver.
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.
Merkulova
T I
TI
Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk 630090, Russia. merkti@niboch.nsc.ru
Kropachev
K Y
KY
Timofeeva
O A
OA
Vasiliev
G V
GV
Ilnitskaya
S I
SI
Levashova
Z B
ZB
Kobzev
V F
VF
Kaledin
V I
VI
D000818:Animals; D001667:Binding, Competitive; D002273:Carcinogens / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051542:Hepatocyte Nuclear Factor 3-beta; D051543:Hepatocyte Nuclear Factor 3-gamma; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013045:Species Specificity; D014157:Transcription Factors; D014444:Tyrosine Transaminase / Q000235:genetics* / Q000378:metabolism*
D002273:Carcinogens; D004268:DNA-Binding Proteins; C496503:Foxa2 protein, mouse; C496504:Foxa2 protein, rat; C496506:Foxa3 protein, mouse; C496507:Foxa3 protein, rat; D005938:Glucocorticoids; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D051543:Hepatocyte Nuclear Factor 3-gamma; D051542:Hepatocyte Nuclear Factor 3-beta; D004247:DNA; D014444:Tyrosine Transaminase