Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (68)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Rose, M. L.
Right arrow Articles by Thurman, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rose, M. L.
Right arrow Articles by Thurman, R. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol 18, 1453-1456, Copyright © 1997 by Oxford University Press

ARTICLES

Kupffer cells are causally responsible for the mitogenic effect of peroxisome proliferators

ML Rose, DR Germolec, R Schoonhoven and RG Thurman
Department of Pharmacology, University of North Carolina, Chapel Hill, USA.

WY-14,643 [4-chloro-6-(2,3-xylidino)pyrimidinylthio-acetic acid] is a well-known non-genotoxic carcinogen and peroxisome proliferator that causes liver cancer in rodents by unknown mechanisms. Its ability to sustain elevated rates of hepatocyte DNA synthesis is most likely pivotal in the ultimate development of tumors. The source of this mitogenic stimulus following treatment of rats with WY-14,643 has been hypothesized to be Kupffer cells, the resident hepatic macrophages, since they are activated by peroxisome proliferators in vivo. Therefore, these studies were designed to determine if Kupffer cells are causally responsible for WY-14 643-induced increases in hepatocyte DNA synthesis in vivo. WY-14,643 (100 mg/kg) increased DNA synthesis 8- fold 24 h after treatment; however, inactivation of Kupffer cells with methyl palmitate, a nonhydrolyzable fatty acid ester and known Kupffer cell inhibitor, completely prevented the mitogenic effect of WY-14,643. On the other hand, the ability of WY-14,643 to induce peroxisomes was not affected by methyl palmitate. These data demonstrate that induction of peroxisomes is not dependent on factors from Kupffer cells and support the idea that stimulation of DNA synthesis and induction of peroxisomes occur via distinct mechanisms. Additionally, WY-14,643 increased liver mRNA transcripts of the hepatocyte mitogen tumor necrosis factor alpha (TNF alpha) more than twofold. This increase was also prevented by inactivating Kupffer cells with methyl palmitate. Therefore, it is concluded that Kupffer cells are causally responsible for WY-14,643-induced increases in hepatocyte DNA synthesis most likely by increasing production of TNF alpha, a hepatic mitogen.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
N. Anderson and J. Borlak
Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis
Pharmacol. Rev., September 1, 2008; 60(3): 311 - 357.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
D. C. Wolf, T. Moore, B. D. Abbott, M. B. Rosen, K. P. Das, R. D. Zehr, A. B. Lindstrom, M. J. Strynar, and C. Lau
Comparative Hepatic Effects of Perfluorooctanoic Acid and WY 14,643 in PPAR-{alpha} Knockout and Wild-type Mice
Toxicol Pathol, June 1, 2008; 36(4): 632 - 639.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C. G. Woods, A. M. Burns, B. U. Bradford, P. K. Ross, O. Kosyk, J. A. Swenberg, M. L. Cunningham, and I. Rusyn
WY-14,643 Induced Cell Proliferation and Oxidative Stress in Mouse Liver are Independent of NADPH Oxidase
Toxicol. Sci., August 1, 2007; 98(2): 366 - 374.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
Q. Yang, S. Ito, and F. J. Gonzalez
Hepatocyte-restricted constitutive activation of PPAR{alpha} induces hepatoproliferation but not hepatocarcinogenesis
Carcinogenesis, June 1, 2007; 28(6): 1171 - 1177.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
R. A. Roberts, P. E. Ganey, C. Ju, L. M. Kamendulis, I. Rusyn, and J. E. Klaunig
Role of the Kupffer Cell in Mediating Hepatic Toxicity and Carcinogenesis
Toxicol. Sci., March 1, 2007; 96(1): 2 - 15.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
R. C. Cattley
Peroxisome Proliferators and Receptor-Mediated Hepatic Carcinogenesis
Toxicol Pathol, February 1, 2004; 32(2_suppl): 6 - 11.
[Abstract] [PDF]

Home page
 CarcinogenesisHome page
T. C. Weglarz and E. P. Sandgren
Cell cross-talk mediates PPAR{alpha} null hepatocyte proliferation after peroxisome proliferator exposure
Carcinogenesis, January 1, 2004; 25(1): 107 - 112.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
J. A. Kramer, E. A.G. Blomme, R. T. Bunch, J. C. Davila, C. J. Jackson, P. F. Jones, K. L. Kolaja, and S. W. Curtiss
Transcription Profiling Distinguishes Dose-Dependent Effects in the Livers of Rats Treated with Clofibrate
Toxicol Pathol, June 1, 2003; 31(4): 417 - 431.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. D. Wheeler, O. M. Smutney, J. F. Check, I. Rusyn, R. Schulte-Hermann, and R. G. Thurman
Impaired Ras membrane association and activation in PPARalpha knockout mice after partial hepatectomy
Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G302 - G312.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
A. M. Siesky, L. M. Kamendulis, and J. E. Klaunig
Hepatic Effects of 2-Butoxyethanol in Rodents
Toxicol. Sci., December 1, 2002; 70(2): 252 - 260.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
R. A. Roberts
Evidence for Cross Talk between PPAR{alpha} and p38 MAP Kinase
Toxicol. Sci., August 1, 2002; 68(2): 270 - 274.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Nakatani, N. Tsuboyama-Kasaoka, M. Takahashi, S. Miura, and O. Ezaki
Mechanism for Peroxisome Proliferator-activated Receptor-alpha Activator-induced Up-regulation of UCP2 mRNA in Rodent Hepatocytes
J. Biol. Chem., March 8, 2002; 277(11): 9562 - 9569.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. P. Anderson, C. S. Dunn, R. C. Cattley, and J.C. Corton
Hepatocellular proliferation in response to a peroxisome proliferator does not require TNF{alpha} signaling
Carcinogenesis, November 1, 2001; 22(11): 1843 - 1851.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. W. Lawrence, G. K. Wollenberg, and J. G. DeLuca
Tumor necrosis factor {{alpha}} is not required for WY14,643-induced cell proliferation
Carcinogenesis, March 1, 2001; 22(3): 381 - 386.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. C. Hasmall, D. A. West, K. Olsen, and R. A. Roberts
Role of hepatic non-parenchymal cells in the response of rat hepatocytes to the peroxisome proliferator nafenopin in vitro
Carcinogenesis, December 1, 2000; 21(12): 2159 - 2165.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. C. Cosulich, N. H. James, M. R.C. Needham, P. P. Newham, K. R. Bundell, and R. A. Roberts
A dominant negative form of IKK2 prevents suppression of apoptosis by the peroxisome proliferator nafenopin
Carcinogenesis, September 1, 2000; 21(9): 1757 - 1760.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I. Rusyn, S. Yamashina, B. H. Segal, R. Schoonhoven, S. M. Holland, R. C. Cattley, J. A. Swenberg, and R. G. Thurman
Oxidants from Nicotinamide Adenine Dinucleotide Phosphate Oxidase Are Involved in Triggering Cell Proliferation in the Liver Due to Peroxisome Proliferators
Cancer Res., September 1, 2000; 60(17): 4798 - 4803.
[Abstract] [Full Text]

Home page
 CarcinogenesisHome page
S. Cosulich, N. James, and R. Roberts
Role of MAP kinase signalling pathways in the mode of action of peroxisome proliferators
Carcinogenesis, April 1, 2000; 21(4): 579 - 584.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
R. T. Miller, S. P. Anderson, J.C. Corton, and R. C. Cattley
Apoptosis, mitosis and cyclophilin-40 expression in regressing peroxisome proliferator-induced adenomas
Carcinogenesis, April 1, 2000; 21(4): 647 - 652.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. M. Peters, I. Rusyn, M. L. Rose, F. J. Gonzalez, and R. G. Thurman
Peroxisome proliferator-activated receptor {alpha} is restricted to hepatic parenchymal cells, not Kupffer cells: implications for the mechanism of action of peroxisome proliferators in hepatocarcinogenesis
Carcinogenesis, April 1, 2000; 21(4): 823 - 826.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. L. Rose, R. C. Cattley, C. Dunn, V. Wong, X. Li, and R. G. Thurman
Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643
Carcinogenesis, November 1, 1999; 20(11): 2075 - 2081.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
I. Rusyn, C. A. Bradham, L. Cohn, R. Schoonhoven, J. A. Swenberg, D. A. Brenner, and R. G. Thurman
Corn oil rapidly activates nuclear factor-{kappa}B in hepatic Kupffer cells by oxidant-dependent mechanisms
Carcinogenesis, November 1, 1999; 20(11): 2095 - 2100.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. B. Barclay, J. M. Peters, M. B. Sewer, L. Ferrari, F. J. Gonzalez, and E. T. Morgan
Modulation of Cytochrome P-450 Gene Expression in Endotoxemic Mice Is Tissue Specific and Peroxisome Proliferator-Activated Receptor-alpha Dependent
J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1250 - 1257.
[Abstract] [Full Text]

Home page
 CarcinogenesisHome page
R. A. Roberts and I. Kimber
Cytokines in non-genotoxic hepatocarcinogenesis
Carcinogenesis, August 1, 1999; 20(8): 1397 - 1402.
[Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. R. Hill, S. Clarke, K. Rodgers, B. Thornhill, J. M. Peters, F. J. Gonzalez, and J. M. Gimble
Effect of Peroxisome Proliferator-Activated Receptor Alpha Activators on Tumor Necrosis Factor Expression in Mice during Endotoxemia
Infect. Immun., July 1, 1999; 67(7): 3488 - 3493.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S Chevalier, N Macdonald, and R. Roberts
Induction of DNA replication by peroxisome proliferators is independent of both tumour necrosis factor (alpha) priming and EGF-receptor tyrosine kinase activity
J. Cell Sci., January 12, 1999; 112(24): 4785 - 4791.
[Abstract] [PDF]

Home page
 CarcinogenesisHome page
M. L. Rose, C. A. Rivera, B. U. Bradford, L. M. Graves, R. C. Cattley, R. Schoonhoven, J. A. Swenberg, and R. G. Thurman
Kupffer cell oxidant production is central to the mechanism of peroxisome proliferators
Carcinogenesis, January 1, 1999; 20(1): 27 - 33.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.