Heme pathway regulation during the initiation stage of hepatocarcinogenesis. Biochemical and molecular findings.

GEREZ, ESTHER; CABALLERO, FABIANA; VAZQUEZ, ELBA; BATLLE, ALCIRA

Hamburgo, Alemania

Simposio; 10th Simposium on Molecular Biology of Hematopoiesis and Treatment of Leukemias and Lymphomas,; 1997

Prof. Dr. Pavel Martaseck

Hepatocarcinogenesis (HC) induced by various carcinogens such as 1,4-dimethylaminoazobenzene (DAB) is a multistep and complex process, and there is a favourite model in rodents that facilitates the study of the mechanisms of chemical carcinogenesis starting from a normal cell and leading to a malignant transformation. Heme regulation before the appearance of hyperplasic nodules was investigated in CF1 mice fed 50 days with DAB (0.5% w/w). Histological studies revealed that DAB produced variations in nuclear size and pleomorphism. As to the biochemical parameters examined DAB provoked the known induction of d-aminolevulinic acid synthase (ALA-S) activity (100%), a diminution (60%) in microsomal heme oxygenase activity and a marked induction (200%) of the cytochrome P450 levels. To study the regulation of ALA-S expression in this model of HC initiation we examined mRNA ALA-S levels in the liver of controls and DAB fed animals. Northern hybridization analysis showed that the mRNA basal levels were increased about 70% in animals treated with DAB. This increase reflected an activation of transcription of the ALA-S gene that correlates well with the induction of this enzyme. Results presented here contribute further to the comprehension of the biological events taking place during the early steps of the HC initiation.