GLUTATHIONE METABOLISM IN PATIENTS WITH NONSMALL CELL LUNG CANCERS

Non-small cen lung cancer (NSCLC) is the leading cause of cancer death in the United States, Because NSCLC is highly chemoresistant, it is u sually not treatable, Altered glutathione (GSH) metabolism is thought to be one major mechanism of chemoresistance, and GSH levels are repor ted to be elevated in NSCLC, Tic main objective of this study is to de lineate the potential mechanisms involved in elevation of tissue GSH, including extraction from the circulation hy NSCLC. Twenty consecutive patients with NSCLC were enrolled, AL the time of lobectomy, pulmonar y artery and vein were identified, and blood now was measured by an el ectromagnetic probe, Subsequently, blood samples were drawn from pulmo nary artery, tile vein draining the tumor-bearing lobe, and a normal l obe. Immediately after lobectomy, tumor and lung specimens were snap f rozen, NSCLC tumor specimens bad higher levels of GSH compared with lu ng tissue (20.8 +/- 9.4 versus 11.6 +/- 3.0 nmol/mg protein, respectiv ely; P < 0.05), The tumor demonstrated higher activity of the enzyme g amma-glutamyl transpeptidase, a membrane-bound enzyme involved in tran smembrane uptake of GSH, than lung tissue (41.9 +/- 26.4 versus 22.4 /- 12.3 units/nag protein, respectivel: P < 0.05), Also, the tumor-bea ring lobe showed elevated extraction of GSH and two of its component a mino acids compared with lung tissue (GSH uptake: 0.60 +/- 0.67 versus 0.20 +/- 0.40 mu M/min, respectively; P < 0.05), NSCLC tumors are abl e to extract circulating GSH and, its constituent amino acids to synth esize intracellular GSH. Increased activity of gamma-glutamyl transpep tidase may be one mechanism underlying increased GSH uptake by NSCLC.