![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 60, Issue 2, 302-309, August 2001
Laboratory of Comparative Carcinogenesis, National Cancer Institute
at National Institute for Environmental Health Sciences (J.L., H.C.,
M.P.W.) and Laboratory of Pharmacology and Chemistry, National
Institute for Environmental Health Sciences, Research Triangle Park,
North Carolina (D.S.M); Intramural Research Support Program, Science
Applications International Corporation (J.E.S.) and Laboratory of
Comparative Carcinogenesis (L.K.K), National Cancer Institute at
Frederick, Frederick, Maryland; and University of Kansas Medical
Center, Kansas City, Kansas (D.R.J, C.D.K.).
Recent work shows that long-term exposure to low levels of arsenite
induces malignant transformation in a rat liver epithelial cell line.
Importantly, these chronic arsenic-exposed (CAsE) cells also develop
self-tolerance to acute arsenic exposure. Tolerance is accompanied by
reduced cellular arsenic accumulation, suggesting a mechanistic basis
for reduced arsenic sensitivity. The present study examined the role of
xenobiotic export pumps in acquired arsenic tolerance. Microarray
analysis of CAsE cells showed increased expression of the genes
encoding for glutathione S-transferase 
(GST-),
multidrug resistance-associated protein genes
(MRP1/MRP2, which encode for the efflux
transporter Mrp1/Mrp2) and the multidrug resistance gene
(MDR1, which encodes for the efflux transporter P-glycoprotein). These findings were confirmed at the transcription level by reverse transcription-polymerase chain reaction and at the
translation level by Western-blot analysis. Acquired arsenic tolerance
was abolished when cells were exposed to ethacrynic acid (an inhibitor
of GST-), buthionine sulfoximine (a glutathione synthesis
inhibitor), MK571 (a specific inhibitor for Mrps), and PSC833 (a
specific inhibitor for P-glycoprotein) in dose-dependent fashions.
MK571, PSC833, and buthionine sulfoximine markedly increased cellular
arsenic accumulation. Consistent with a role for multidrug resistance
efflux pumps in arsenic resistance, CAsE cells were found to be
cross-resistant to cytotoxicity of several anticancer drugs, such as
vinblastine, doxorubicin, actinomycin-D, and cisplatin, that are also
substrates for Mrps and P-glycoprotein. Thus, acquired tolerance to
arsenic is associated with increased expression GST-, Mrp1/Mrp2 and
P-glycoprotein, which function together to reduce cellular arsenic accumulation.
This article has been cited by other articles:
|
|
 |
|
  J. Liu and M. P. Waalkes Liver is a Target of Arsenic Carcinogenesis Toxicol. Sci., September 1, 2008; 105(1): 24 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-F. Coppin, W. Qu, and M. P. Waalkes Interplay between Cellular Methyl Metabolism and Adaptive Efflux during Oncogenic Transformation from Chronic Arsenic Exposure in Human Cells J. Biol. Chem., July 11, 2008; 283(28): 19342 - 19350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Norton, D. E. Lou-Hing, A. A. Meharg, and A. H. Price Rice-arsenate interactions in hydroponics: whole genome transcriptional analysis J. Exp. Bot., May 2, 2008; (2008) ern097v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wu, J. Liu, M. P. Waalkes, M.-L. Cheng, L. Li, C.-X. Li, and Q. Yang High Dietary Fat Exacerbates Arsenic-Induced Liver Fibrosis in Mice Experimental Biology and Medicine, March 1, 2008; 233(3): 377 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Lee, C. Y. Han, J. W. Yang, C. Smith, S. K. Kim, E. Y.-H. P. Lee, S. G. Kim, and K. W. Kang Induction of Glutathione Transferase in Insulin-Like Growth Factor Type I Receptor-Overexpressed Hepatoma Cells Mol. Pharmacol., October 1, 2007; 72(4): 1082 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Sun, S. Zhang, J. Y. Chan, and D. D. Zhang Keap1 Controls Postinduction Repression of the Nrf2-Mediated Antioxidant Response by Escorting Nuclear Export of Nrf2 Mol. Cell. Biol., September 15, 2007; 27(18): 6334 - 6349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Miller, J. R. Shaw, C. R. Stanton, R. Barnaby, K. H. Karlson, J. W. Hamilton, and B. A. Stanton MRP2 and Acquired Tolerance to Inorganic Arsenic in the Kidney of Killifish (Fundulus heteroclitus) Toxicol. Sci., May 1, 2007; 97(1): 103 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kool, M. Eggink, H. van Rossum, S. M. van Liempd, D. A. van Elswijk, H. Irth, J. N.M. Commandeur, J. H.N. Meerman, and N. P.E. Vermeulen Online Biochemical Detection of Glutathione-S-Transferase P1-Specific Inhibitors in Complex Mixtures J Biomol Screen, April 1, 2007; 12(3): 396 - 405. [Abstract] [PDF]
|
|
|
|
 |
|
 J. R. Shaw, K. Gabor, E. Hand, A. Lankowski, L. Durant, R. Thibodeau, C. R. Stanton, R. Barnaby, B. Coutermarsh, K. H. Karlson, et al. Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R1052 - R1060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Lam, C. L. Winata, Y. Tong, S. Korzh, W. S. Lim, V. Korzh, J. Spitsbergen, S. Mathavan, L. D. Miller, E. T. Liu, et al. Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver Physiol Genomics, November 21, 2006; 27(3): 351 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kimura, Y. Ishida, T. Hayashi, T. Wada, H. Yokoyama, T. Sugaya, N. Mukaida, and T. Kondo Interferon-{gamma} Plays Protective Roles in Sodium Arsenite-Induced Renal Injury by Up-Regulating Intrarenal Multidrug Resistance-Associated Protein 1 Expression Am. J. Pathol., October 1, 2006; 169(4): 1118 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-C. Lee, I-C. Ho, W.-J. Lu, and J.-d. Huang Enhanced Expression of Multidrug resistance-associated Protein 2 and Reduced Expression of Aquaglyceroporin 3 in an Arsenic-resistant Human Cell Line J. Biol. Chem., July 7, 2006; 281(27): 18401 - 18407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Argos, M. G. Kibriya, F. Parvez, F. Jasmine, M. Rakibuz-Zaman, and H. Ahsan Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a bangladeshi population. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1367 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kojima, W. Qu, M. P. Waalkes, S. Himeno, and T. Sakurai Chronic Exposure to Methylated Arsenicals Stimulates Arsenic Excretion Pathways and Induces Arsenic Tolerance in Rat Liver Cells Toxicol. Sci., May 1, 2006; 91(1): 70 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rana and T. Allen Influence of thyroxine and n-propylthiouracil on nephro-toxicity of inorganic arsenic in rat Toxicology and Industrial Health, April 1, 2006; 22(3): 137 - 145. [Abstract] [PDF]
|
|
|
|
 |
|
 A. M. Ramos, C. Fernandez, D. Amran, P. Sancho, E. de Blas, and P. Aller Pharmacologic inhibitors of PI3K/Akt potentiate the apoptotic action of the antileukemic drug arsenic trioxide via glutathione depletion and increased peroxide accumulation in myeloid leukemia cells Blood, May 15, 2005; 105(10): 4013 - 4020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhou, Y. Jing, M. Styblo, Z. Chen, and S. Waxman Glutathione-S-transferase {pi} inhibits As2O3-induced apoptosis in lymphoma cells: involvement of hydrogen peroxide catabolism Blood, February 1, 2005; 105(3): 1198 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cui, Y. Kobayashi, T. Hayakawa, and S. Hirano Arsenic Speciation in Bile and Urine Following Oral and Intravenous Exposure to Inorganic and Organic Arsenics in Rats Toxicol. Sci., December 1, 2004; 82(2): 478 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Annereau, G. Szakacs, C. J. Tucker, A. Arciello, C. Cardarelli, J. Collins, S. Grissom, B. R. Zeeberg, W. Reinhold, J. N. Weinstein, et al. Analysis of ATP-Binding Cassette Transporter Expression in Drug-Selected Cell Lines by a Microarray Dedicated to Multidrug Resistance Mol. Pharmacol., December 1, 2004; 66(6): 1397 - 1405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Drummelsmith, I. Girard, N. Trudel, and M. Ouellette Differential Protein Expression Analysis of Leishmania major Reveals Novel Roles for Methionine Adenosyltransferase and S-Adenosylmethionine in Methotrexate Resistance J. Biol. Chem., August 6, 2004; 279(32): 33273 - 33280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Leslie, A. Haimeur, and M. P. Waalkes Arsenic Transport by the Human Multidrug Resistance Protein 1 (MRP1/ABCC1): EVIDENCE THAT A TRI-GLUTATHIONE CONJUGATE IS REQUIRED J. Biol. Chem., July 30, 2004; 279(31): 32700 - 32708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Vickers and A. H. Fairlamb Trypanothione S-Transferase Activity in a Trypanosomatid Ribosomal Elongation Factor 1B J. Biol. Chem., June 25, 2004; 279(26): 27246 - 27256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, C. Li, W. Qu, E. Leslie, C. L. Bonifant, G. S. Buzard, J. E. Saavedra, L. K. Keefer, and M. P. Waalkes Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation Mol. Cancer Ther., June 1, 2004; 3(6): 709 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Depeille, P. Cuq, S. Mary, I. Passagne, A. Evrard, D. Cupissol, and L. Vian Glutathione S-Transferase M1 and Multidrug Resistance Protein 1 Act in Synergy to Protect Melanoma Cells from Vincristine Effects Mol. Pharmacol., April 1, 2004; 65(4): 897 - 905. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. T Leussink, H. J Baelde, T. M B.-v. den Berg, E. de Heer, G. B van der Voet, A. Slikkerveer, J. A Bruijn, and F. A de Wolff Renal epithelial gene expression profile and bismuth-induced resistance against cisplatin nephrotoxicity Human and Experimental Toxicology, October 1, 2003; 22(10): 535 - 540. [Abstract] [PDF]
|
|
|
|
|
|
O. Briz, R. I. R. Macias, M. Vallejo, A. Silva, M. A. Serrano, and J. J. G. Marin Usefulness of Liposomes Loaded with Cytostatic Bile Acid Derivatives to Circumvent Chemotherapy Resistance of Enterohepatic Tumors Mol. Pharmacol., March 1, 2003; 63(3): 742 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Achanzar, E. M. Brambila, B. A. Diwan, M. M. Webber, and M. P. Waalkes Inorganic Arsenite-Induced Malignant Transformation of Human Prostate Epithelial Cells J Natl Cancer Inst, December 18, 2002; 94(24): 1888 - 1891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Bahlis, J. McCafferty-Grad, I. Jordan-McMurry, J. Neil, I. Reis, M. Kharfan-Dabaja, J. Eckman, M. Goodman, H. F. Fernandez, L. H. Boise, et al. Feasibility and Correlates of Arsenic Trioxide Combined with Ascorbic Acid-mediated Depletion of Intracellular Glutathione for the Treatment of Relapsed/Refractory Multiple Myeloma Clin. Cancer Res., December 1, 2002; 8(12): 3658 - 3668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Qu, C. D. Bortner, T. Sakurai, M. J. Hobson, and M. P. Waalkes Acquisition of apoptotic resistance in arsenic-induced malignant transformation: role of the JNK signal transduction pathway Carcinogenesis, January 1, 2002; 23(1): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
