MAIN DRUG-METABOLIZING AND CARCINOGEN-METABOLIZING ENZYME-SYSTEMS IN HUMAN NONSMALL CELL LUNG-CANCER AND PERITUMORAL TISSUES

To better understand the importance of drug-metabolizing enzymes in ca rcinogenesis and anticancer drug sensitivity of human non-small cell l ung cancer, we studied the main drug-metabolizing enzyme systems in bo th lung tumors and their corresponding nontumoral lung tissues in 12 p atients. The following enzymes were assayed by Western blot analysis: cytochromes P-450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4); epoxide hydrolas e; and glutathione S-transferase isoenzymes (GST-alpha, -mu and -pi). The activity of the following enzymes or cofactor were determined by s pectrophotometric or fluorometric assays: glutathione S-transferase (G ST); total glutathione; UDP-glucuronosyltransferase; beta-glucuronidas e, sulfotransferase; and sulfatase. Results showed the presence of cyt ochrome P-450 1A1/1A2 in both tumoral and nontumoral tissues. P-450 1A 1/1A2 levels were 3-fold lower in tumors compared to corresponding non tumoral tissues (P < 0.05). None of the other probed cytochromes P-450 were detected in either tumoral or nontumoral lung tissues. For the g lutathione system, no significant difference between tumoral and nontu moral tissues was observed (GST activity, glutathione content, GST-alp ha, -mu, and -pi). A positive linear correlation was observed between GST activity and GST-alpha or GST-pi. No significant difference was ob served for the glucuronide and the sulfate pathways and their correspo nding hydrolytic enzymes. Epoxide hydrolase was significantly decrease d in tumors compared to nontumoral lung tissues (P < 0.05). In conclus ion, these results showed differences between non-small cell lung tumo rs and nontumoral tissues for cytochrome P-450 1A1/1A2 and epoxide hyd rolase. These differences between tumors and peritumoral tissues with regard to these drug-metabolizing enzymes could reflect differences oc curring after malignant transformation and may play a role in drug sen sitivity to anticancer drugs.