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.