The Role of Aryl Hydrocarbon Receptor-Regulated Cytochrome P450 Enzymes in Glioma

Glioma is still one of the most aggressive forms of brain tumors. Understanding of the biological and pathophysiological mechanisms of survival can help the researchers to develop new management modalities. Industrial toxins could be one of the most important causes for brain tumors, such as dioxin and other aryl hydrocarbon receptor (AhR) ligands. Toxicity of these compounds includes a series of cellular events starting from binding with AhR and ending with the increased expression of a group of xenobiotic metabolizing enzymes (XME) such as the cytochrome P450 (CYPs), CYP1A1, CYP1A2, and CYP1B1. Therefore, identification of the localizations and expressions of the AhR and its regulated CYPs in the central nervous system (CNS) and neuronal cells is of major importance in understanding their physiological and pathological roles. Generally, low but significant level of CYPs expression is demonstrated in the brain in a tissue- and species-specific manner. Moreover, most, but not all, AhR-regulated CYPs are expressed differently in most of the neuronal and glial cells. Although the exact mechanisms of AhR-mediated glioma and neurotoxicity are not fully understood, the present review proposes several mechanisms which include generating reactive oxygen species, activating glutamate receptors, peroxisome proliferator- activated receptors, histone acetylation, and signal transducer and activator of transcription 3.