Abstracts
1999 Digestive Disease Week

# 2146 GLUTATHIONE AND TRANSFORMING GROWTH FACTOR ALPHA (TGF-a)-DEPENDENT PROLIFERATION OF THE PANCREATIC ADENOCARCINOMA CELL LINE ASPC-1
Thomas Schnelldorfer, S Gansauge, F Gansauge, G Leder, H G Beger, A K Nussler, Univ of Ulm, Ulm Germany

Recent evidence suggest that glutathione (GSH) and the overexpression of angiogenetic factors such as TGF-a are crucial in the proliferation of various tumors. In the same line of evidence, it has been shown thst EGF enhances GSH synthesis in a human breast cancer cell line. Therefore, it is conceivable that in tumors the mitogen-dependent GSH synthesis may function on two levels: i) triggering the cell proliferation and ii) protecting against the host immune response (e.g., oxidative stress). In the present study, we investigated the interrelationship of TGF-a and GSH via the cell cycle in the human adenocarcinoma cell line AsPC-1. Cells were incubated either with a single dose of TGF-a (25 ng/ml) or a continuous TGF-a exposure in the presence or absence of the GSH depleting agent BSO. Cell cycle analysis, proliferation tests (BrdU-assay) as well as GSH levels (during G1/G0, G1/Go to S-phase, G2/M-phase) were measured at different time points. In addition, we investigated the GSH contents in normal human pancreatic tissue (n=10) and pancreatic adenocarcinomas (n=15). We found that basic GSH levels were high in AsPC-1 cells (48.2±12.3 nmol/mg protein) and were not further significantly increased in the presence of a single or continues dose of TGF-a. When cells were depleted of GSH, the TGF-a-mediated cell cycle stimulation was inhibited, while in the absence of TGF-a cell proliferation was unchanged. The crucial role of GSH was further confirmed by elevated levels in pancreatic carcinoma tissue compaired with normal pancreatic tissue (16.1±8.5 vs. 8.5±4.2 nmol/mg protein; p=0.007). We conclude from our results that for the proliferation of the adenocarcinoma cell line AsPC-1, TGF-a as well as GSH are necessary. Furthermore, the elevated levels of GSH in tumors might have an additional role by protecting the tumor from cytotoxic macrophage or radiotherapy-mediated radical injury.

Copyright 1996 - 1999, SSAT, Inc.