Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

Abstract

Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.

Functional role and tobacco smoking effects on methylation ofCYP1A1gene in prostate cancer

“…esophagus, breast, urinary bladder, and brain tumor, and is associated with poor prognosis [32–36]. These findings are conceivable since CYP1A1 is known to play an important role in the formation of PAH-DNA adducts which may induce mutations in several cancer-related genes that contribute to carcinogenesis [37, 38].…”

Brief Descriptive Epidemiology of Primary Malignant Brain Tumors from North-East India

“…Case-control study on small number of patients with brain tumors have shown altered expression of xenobiotic metabolizing genes (Wahid et al, 2013). Brain tumors are rare, so case-control analytic epidemiological studies will be required to establish the risk factors prevalent in our population.…”

Prognostic Significance of Altered Blood and Tissue Glutathione Levels in Head and Neck Squamous Cell Carcinoma Cases

“…Present results from this study have shown that levels of glutathione are decreased in blood of head and neck cancer patients and elevated in tissues when compared to the respective controls. These decreased and elevated levels of glutathione may deregulate cytochrome P450 (Wahid et al, 2013) and glutathione expression which are important mechanisms involved in carcinogenesis and mutagenesis. GSH is among the most efficient substance which can be used by cells and tissues in their defense against oxidative stress and is representative of redox environment of the cell (Cacciatore et al, 2010).…”