The role of aryl hydrocarbon receptor in regulation of enzymes involved in metabolic activation of polycyclic aromatic hydrocarbons in a model of rat liver progenitor cells.

In contrast to hepatocytes, there is only limited information about the expression and activities of enzymes participating in metabolic activation of environmental mutagens, including polycyclic aromatic hydrocarbons (PAHs), in liver progenitor cells. In rat liver "stem-like" WB-F344 cell line, sharing many characteristics with rat liver progenitor cells, PAHs are efficiently activated to their ultimate genotoxic metabolites forming DNA adducts. The present study aimed to characterize expression/activities of enzymes of two major pathways involved in the metabolism of benzo[a]pyrene (BaP): cytochrome P450 (CYP) family 1 enzymes and cytosolic aldo-keto reductases (AKRs).

Reduction of doxorubicin and oracin and induction of carbonyl reductase in human breast carcinoma MCF-7 cells.

In cancer cells, the drug-metabolizing enzymes may deactivate cytostatics, thus contributing to their survival. Moreover, the induction of these enzymes may also contribute to development of drug-resistance through acceleration of cytostatics deactivation. However, the principal metabolic pathways contributing to deactivation of many cytostatics still remain poorly defined.