BCL-2 AND BCL-X(L) IN PEROXIDE-RESISTANT A549 AND U87MG CELLS

Overexpression of the bcl-2 and the related bcl-x(L) protooncogene pro teins enhance cell survival by inhibiting apoptosis induced by many ag ents including oxidants. Whether these proteins contribute to survival in oxidant-resistant cells is not known. The current study assessed t he expression of bcl-2 and bcl-x(L) proteins in human glioblastoma U87 MG cells and human lung adenocarcinoma A549 cells selected for resista nce to 0, 50, 100, 200, and 400 mu M H2O2 by exposure to this oxidant one time each passage for 9 months. When examined 7 to 32 days after c essation of peroxide exposure (times when peroxide resistance was main tained), bcl-2 protein levels were significantly increased in most per oxide-resistant U87MG cells. However, the increase was not dose depend ent and was not accompanied by an increase in mKNA levels. A549 cells did not express significant levels of bcl-2 protein, although bcl-2 mR NA was detectable. A549 cells expressed large amounts of bcl-x(L) and immunohistochemistry demonstrated extensive localization of this prote in around the nucleus. However, expression of this protein was not alt ered in peroxide-resistant lines nor was bcl-2 protein increased to a measurable level. U87MG cells also expressed bcl-x(L) but it was not a ltered in peroxide-resistant cells. Although the increased bcl-2 prote in in peroxide-resistant U87MG cells may contribute to their oxidant t olerance, the lack of a dose-response relationship, the failure to ind uce bcl-x(L) protein, and the absence of any bcl-2 or bcl-x(L) protein induction in peroxide-resistant A549 cells suggest these genes are no t primary factors in oxidant resistance. (C) 1998 Society of Toxicolog y.