| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Carcinogenesis |
Department of Toxicology, Oncology and Molecular Pathology Unit, University of Cagliari, 09124 Cagliari, Italy [G. M. L-C., A. P., R. L., A. C.], and Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 [H. S.]
Previous studies have demonstrated that short-term treatment with
peroxisome proliferators decreased the size and number of 
-glutamyl
transpeptidase or placental glutathione S-transferase
(GSTP)-positive hepatic hyperplastic lesions. In this study, we have
examined the effect of the hormone triiodothyronine (T3), which,
similarly to peroxisome proliferators, is a strong liver mitogen and a
ligand of nuclear receptors, on the growth of GSTP-positive nodules
generated by the resistant hepatocyte model and on the development of
hepatocellular carcinoma. Hepatic hyperplastic nodules were induced in
male Fischer rats by a single dose (150 mg/kg) of diethylnitrosamine,
followed by a 2-week exposure of the animals to 2-acetylaminofluorene
and partial hepatectomy. Nine weeks after diethylnitrosamine
administration, rats were switched to a diet containing 4 mg/kg T3 for
1 week (experiment 1) and sacrificed during T3 feeding or were exposed
to seven cycles of T3-supplemented diet (1 week/month per 7 months),
and sacrificed 6 months after the last cycle (experiment 2). Results
showed that T3 treatment for 1 week caused a 70% reduction in the
number of GSTP-positive nodules (14/cm2 in T3-fed rats
versus 44/cm2 of control animals), as well
as GSTP-positive area (12% versus 43% of controls).
Reduction in the number of GSTP-positive nodules observed 1 week after
T3 feeding was associated with a strong increase in the labeling index
of enzyme-altered nodules compared with that of controls (labeling
index was 64 and 31%, respectively). No significant differences in the
apoptotic index were observed between the two groups. Results from
experiment 2 did reveal that although rats treated with
diethylnitrosamine + 2-acetylaminofluorene developed 100%
hepatocellular carcinoma and 33% of them showed lung metastasis, only
50% of rats exposed to repeated cycles of triiodothyronine developed
hepatocellular carcinoma with no lung metastasis. This study indicates
that cell proliferation per se might not necessarily
represent a promoting condition for putative preneoplastic lesions and
demonstrates an anticarcinogenic effect of T3.
This article has been cited by other articles:
|
|
 |
|
  K. Kubota, J. Soeda, R. Misawa, M. Mihara, S. Miwa, H. Ise, M. Takahashi, and S. Miyagawa Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model Carcinogenesis, February 1, 2008; 29(2): 448 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Perra, M. Pibiri, P. Sulas, G. Simbula, G. M. Ledda-Columbano, and A. Columbano {alpha}-lipoic acid promotes the growth of rat hepatic pre-neoplastic lesions in the choline-deficient model Carcinogenesis, January 1, 2008; 29(1): 161 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Michienzi, B. Bucci, C. Verga Falzacappa, V. Patriarca, A. Stigliano, L. Panacchia, E. Brunetti, V. Toscano, and S. Misiti 3,3',5-Triiodo-L-thyronine inhibits ductal pancreatic adenocarcinoma proliferation improving the cytotoxic effect of chemotherapy J. Endocrinol., May 1, 2007; 193(2): 209 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fava, Y. Ueno, S. Glaser, H. Francis, S. DeMorrow, L. Marucci, M. Marzioni, A. Benedetti, J. Venter, B. Vaculin, et al. Thyroid hormone inhibits biliary growth in bile duct-ligated rats by PLC/IP3/Ca2+-dependent downregulation of SRC/ERK1/2 Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1467 - C1475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Columbano, M. Pibiri, M. Deidda, C. Cossu, T. S. Scanlan, G. Chiellini, S. Muntoni, and G. M. Ledda-Columbano The Thyroid Hormone Receptor-{beta} Agonist GC-1 Induces Cell Proliferation in Rat Liver and Pancreas Endocrinology, July 1, 2006; 147(7): 3211 - 3218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Yen, Y.-H. Huang, C.-Y. Liao, C.-J. Liao, W.-L. Cheng, W.-J. Chen, and K.-H. Lin Mediation of the inhibitory effect of thyroid hormone on proliferation of hepatoma cells by transforming growth factor-beta J. Mol. Endocrinol., February 1, 2006; 36(1): 9 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. de Almeida Vasconcelos Fonseca, C. E. A. Chagas, R. P. Mazzantini, R. Heidor, T. P. Ong, and F. S. Moreno All-trans and 9-cis retinoic acids, retinol and {beta}-carotene chemopreventive activities during the initial phases of hepatocarcinogenesis involve distinct actions on glutathione S-transferase positive preneoplastic lesions remodeling and DNA damage Carcinogenesis, November 1, 2005; 26(11): 1940 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G M Ledda-Columbano, A Perra, M Pibiri, F Molotzu, and A Columbano Induction of pancreatic acinar cell proliferation by thyroid hormone J. Endocrinol., June 1, 2005; 185(3): 393 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hayashi, T. Tamura, J. Kuroda, H. Ohnota, N. Shibata, M. Akahane, Y. Kashida, and K. Mitsumori Different Inhibitory Effects in the Early and Late Phase of Treatment with KAT-681, a Liver-Selective Thyromimetic, on Rat Hepatocarcinogenesis Induced by 2-Acetylaminofluorene and Partial Hepatectomy after Diethylnitrosamine Initiation Toxicol. Sci., March 1, 2005; 84(1): 22 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.M. Ledda-Columbano, M. Pibiri, F. Molotzu, C. Cossu, L. Sanna, G. Simbula, A. Perra, and A. Columbano Induction of hepatocyte proliferation by retinoic acid Carcinogenesis, November 1, 2004; 25(11): 2061 - 2066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Ledda-Columbano, A. Perra, D. Concas, C. Cossu, F. Molotzu, C. Sartori, H. Shinozuka, and A. Columbano Different Effects of the Liver Mitogens Triiodo-Thyronine and Ciprofibrate on the Development of Rat Hepatocellular Carcinoma Toxicol Pathol, January 1, 2003; 31(1): 113 - 120. [Abstract] [PDF]
|
|
|
|
|
|
P. Bannasch, T. Haertel, and Qin Su Significance of Hepatic Preneoplasia in Risk Identification and Early Detection of Neoplasia Toxicol Pathol, January 1, 2003; 31(1): 134 - 139. [Abstract] [PDF]
|
|
|
|
|
|
M. Evert, T. Ott, A. Temme, K. Willecke, and F. Dombrowski Morphology and morphometric investigation of hepatocellular preneoplastic lesions and neoplasms in connexin32-deficient mice Carcinogenesis, May 1, 2002; 23(5): 697 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Wood, J. E. Korkola, and M. C. Archer Tissue-specific resistance to cancer development in the rat: phenotypes of tumor-modifier genes Carcinogenesis, January 1, 2002; 23(1): 1 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xu, L. Hui, S. Wang, J. Gong, Y. Jin, Y. Wang, Y. Ji, X. Wu, Z. Han, and G. Hu Expression Profiling Suggested a Regulatory Role of Liver-enriched Transcription Factors in Human Hepatocellular Carcinoma Cancer Res., April 1, 2001; 61(7): 3176 - 3181. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
