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© 1998 Oxford University Press
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Bcl-2 and Bcl-xL in Peroxide-Resistant A549 and U87MG Cells



*Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin Austin, Texas 78712-1074
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University West Lafayette, Indiana 47907
Section of Cancer Biology, Radiation Oncology Center, Washington University School of Medicine St. Louis, Missouri 63108
Received October 3, 1997; accepted December 12, 1997
Overexpression of the bcl-2 and the related bcl-xL protoonco-gene proteins enhance cell survival by inhibiting apoptosis induced by many agents including oxidants. Whether these proteins contribute to survival in oxidant-resistant cells is not known. The current study assessed the expression of bcl-2 and bcl-xL proteins in human glioblastoma U87MG cells and human lung adenocar-cinoma A549 cells selected for resistance to 0, 50, 100, 200, and 400 µM H2O2 by exposure to this oxidant one time each passage for 9 months. When examined 7 to 32 days after cessation of peroxide exposure (times when peroxide resistance was maintained), bcl-2 protein levels were significantly increased in most peroxide-resistant U87MG cells. However, the increase was not dose dependent and was not accompanied by an increase in mRNA levels. A549 cells did not express significant levels of bcl-2 protein, although bcl-2 mRNA was detectable. A549 cells expressed large amounts of bcl-xL and immunohistochemistry demonstrated extensive localization of this protein around the nucleus. However, expression of this protein was not altered in peroxide-resistant lines nor was bcl-2 protein increased to a measurable level. U87MG cells also expressed bcl-xL but it was not altered in peroxide-resistant cells. Although the increased bcl-2 protein in peroxide-resistant U87MG cells may contribute to their oxidant tolerance, the lack of a dose-response relationship, the failure to induce bcl-xL protein, and the absence of any bcl-2 or bcl-xL protein induction in peroxide-resistant A549 cells suggest these genes are not primary factors in oxidant resistance.
Key Words: bcl-2; bcl-xL; hydrogen peroxide; oxidant toxicity; A549 cells; U87MG cells.
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