This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chao Yeh, G. Articles by Phang, J. M. Search for Related Content PubMed PubMed Citation Articles by Chao Yeh, G. Articles by Phang, J. M.

A New Functional Role for P-Glycoprotein: Efflux Pump for Benzo(a)pyrene in Human Breast Cancer MCF-7 Cells

Laboratory of Nutritional and Molecular Regulation, Division of Cancer Prevention and Control, National Cancer Institute, NIH, Frederick, Maryland 21702

¹ To whom requests for reprints should be addressed, at LNMR Bldg. 560, Room 12-48, NCI-FCRDC, Frederick, MD 21702.

We propose that the cellular burden of certain carcinogens may be mitigated by P-glycoprotein (P-gp), the putative drug efflux pump. In a series of multidrug resistant human breast cancer MCF-7 cells with increasing P-gp expression we examined this hypothesis using benzo(a)pyrene, a widely distributed environmental and dietary carcinogen. We found that multidrug resistant cells were cross-resistant to benzo(a)pyrene and the rates of efflux for benzo(a)pyrene were higher in multidrug resistant cells than in wild type cells. Evidence supporting the involvement of P-gp included the inhibition of azidopine binding to P-gp benzo(a)pyrene and the inhibition of benzo(a)pyrene efflux by Adriamycin and verapamil. Our findings suggest that P-gp may play a role in the cellular defense to carcinogens. The expression of P-gp and the modulation of its function may affect the susceptibility of normal tissues to transformation by carcinogens.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/28/92. Accepted 10/13/92.

This article has been cited by other articles:

				B. J. Albert, P. A. McPherson, K. O'Brien, N. L. Czaicki, V. DeStefino, S. Osman, M. Li, B. W. Day, P. J. Grabowski, M. J. Moore, et al. Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells Mol. Cancer Ther., August 1, 2009; 8(8): 2308 - 2318. [Abstract] [Full Text] [PDF]

				B. Ebert, A. Seidel, and A. Lampen Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists Carcinogenesis, October 1, 2005; 26(10): 1754 - 1763. [Abstract] [Full Text] [PDF]

				J. Albertus and R. Laine Enhanced xenobiotic transporter expression in normal teleost hepatocytes: response to environmental and chemotherapeutic toxins J. Exp. Biol., January 1, 2001; 204(2): 217 - 227. [Abstract] [PDF]

				D. W. Loe, R. K. Stewart, T. E. Massey, R. G. Deeley, and S. P. C. Cole ATP-Dependent Transport of Aflatoxin B1 and Its Glutathione Conjugates by the Product of the Multidrug Resistance Protein (MRP) Gene Mol. Pharmacol., June 1, 1997; 51(6): 1034 - 1041. [Abstract] [Full Text]