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


Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobioticprocessing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites aregenerally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymesdetermines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certainconditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolitesthat can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed totest the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile ofmetabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controlsusing Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same studycohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as comparedto the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expressionof GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). Thisdown 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 tocontrols. 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 metabolizinggenes may be involved in brain tumor development in Pakistani population. Investigation of expression of thesegenes may provide information not only for the prediction of individual cancer risk but also for the preventionof cancer.