OAT and 3'MeDAB azo compounds similarly cause liver tumors in GR mice, but differently modify activities of FoxA transcription factors.
Transcription factors of the FoxA family (forkhead box A) regulate cell metabolism and differentiation and maintain specificity of liver cell proteome and phenotype of mature hepatocytes. The relationship between hepatocarcinogenicity of azo compounds o-aminoazotoluene (OAT) and 3'-methyl-4-dimethylaminobenzene (3'MeDAB) for GR mice and one of the early events, modulation of the DNA-binding activity of FoxA transcription factor, was studied. Single injection of 3'MeDAB to 12-day-old mice caused liver tumors in 100% males and females similarly as OAT, a well-known mouse hepatocarcinogene. The DNA-binding activity of FoxA in the liver decreased 2.5-3 times by OAT, this resulting in a 40% reduction of glucocorticoid induction of tyrosine aminotransferase (liver-specific gene). In contrast to these, 3'MeDAB did not modify FoxA protein activities or the degree of glucocorticoid induction of tyrosine aminotransferase.
Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia. pmaria@yandex.ru
M Yu
MY
Pakharukova
M A
MA
Smetanina
S I
SI
Ilnitskaya
V I
VI
Kaledin
T I
TI
Merkulova
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology / Q000633:toxicity*; D001555:Benzene Derivatives / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids; D051536:Hepatocyte Nuclear Factors / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D009762:o-Aminoazotoluene / Q000494:pharmacology / Q000633:toxicity*
C473128:3'-methyl 4-dimethylazobenzene; D001391:Azo Compounds; D001555:Benzene Derivatives; D005938:Glucocorticoids; D051536:Hepatocyte Nuclear Factors; D050783:Proto-Oncogene Proteins c-ets; D009762:o-Aminoazotoluene