ABSTRACT
It is known that the carcinogenic effect of estragole, a component of essential oils of many spicy plants, is characterized by species, tissue, and sex specificity. It causes mainly liver tumors in female mice but is not carcinogenic for male mice and for rats. In this work, the estragole hepatocarcinogenicity was shown for female mice of previously not studied ICR line. The strict correlation between estragole hepatocarcinogenicity and its ability to decrease the level of glucocorticoid induction of liver-specific enzymes tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO) was found. Inhibition of TAT and TO inducibility by estragole takes place only in female mice but not in male mice and in rats. Studying the estragole effect on DNA-binding activity of transcription factors, present mainly in liver and regulating expression of genes encoding liver-specific proteins, has shown that estragole decreases FOXA and HNF4 activities but not activities of C/EBP and HNF1, and this happens only in female mice, for which this substance is hepatocarcinogen, but not in male mice and in rats. Pentachlorophenol, preventing hepatocarcinogenic effect of estragole, abolishes inhibitory influence of the latter on the TAT and TO glucocorticoid induction and restores DNA-binding activity of FOXA and HNF4. Thus, a correlation was revealed between the estragole hepatocarcinogenic effect and decrease in DNA-binding activity of transcription factors FOXA and HNF4, which might be indicative of the role of these factors in tumor suppression mechanisms in liver.
Subject(s)
Anisoles/pharmacology , Carcinogens/pharmacology , Forkhead Transcription Factors/metabolism , Glucocorticoids/metabolism , Hepatocyte Nuclear Factor 4/metabolism , Liver/drug effects , Liver/enzymology , Allylbenzene Derivatives , Animals , Female , Forkhead Transcription Factors/genetics , Hepatocyte Nuclear Factor 4/genetics , Liver/metabolism , Male , Mice , Mice, Inbred ICR , Rats , Rats, Wistar , Sex Characteristics , Species Specificity , Tryptophan Oxygenase/metabolism , Tyrosine Transaminase/metabolismABSTRACT
Here we describe an experimental tumor, hepatocarcinoma-29: transplantable strain of this tumor is maintained in an ascitic form in CBA/LacYIcgn mice in Institute of Cytology and Genetics of SD of RAS. After inoculation into the thigh muscles, the tumor induces anorexia, progressing loss of fat and muscle tissues, and physiological changes specific for cachexia: leukocytosis, hypoglycemia, and hypercorticism. The tumor metastasizes to all vital viscera and leads to animal death from renal failure.
Subject(s)
Cachexia/pathology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Transplantation/methods , Neoplasms, Experimental , Animals , Disease Models, Animal , Male , Mice , Neoplasm MetastasisABSTRACT
o-Aminoazotoluene in noncarcinogenic doses promoted the development of liver tumors in female ICR mice induced by administration of diethylnitrosamine during early ontogeny. Severe inflammatory infiltration and proliferation of oval cells were found in liver tissue of these animals. The concentration of free thyroxin decreased in the blood. Our results supplement published data that promoters of hepatocarcinogenesis inhibit thyroid function.
