Carcinogenesis, Vol. 23, No. 5, 787-794,
May 2002
© 2002 Oxford University Press
MOLECULAR EPIDEMIOLOGY |
Dietary silymarin suppresses 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats
1 Department of Laboratory Sciences, School of Health Sciences, Faculty of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942,
2 Department of Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 and
3 Department of Pathology, Gifu University School of Medicine, 40 Tsuksa-machi, Gifu 500-8705, Japan
Abstract
The modifying effect of dietary administration of a polyphenolic antioxidant flavonoid silymarin isolated milk thistle [Silybum marianum (L.) Gaertneri] on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis was investigated in male F344 rats. Based on the results in pilot studies showing that silymarin treatment together with 4-NQO significantly reduced the occurrence of tongue dysplasia and gavaged with silymarin significantly elevated the phase II detoxifying enzymes' activities in the liver and tongue, the effects of dietary feeding of silymarin on tongue carcinogenesis were investigated in a long-term experiment, where rats were initiated with 4-NQO and fed silymarin containing diets during or after 4-NQO exposure. At 5 weeks of age, all animals except those treated with silymarin alone and untreated rats were given 20 p.p.m. 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 1 week before 4-NQO administration, animals were fed the experimental diets containing silymarin (100 and 500 p.p.m.) for 10 weeks, and then maintained on a basal diet for 24 weeks. Starting 1 week after the cessation of 4-NQO exposure, the experimental groups given 4-NQO and a basal diet were fed the experimental diets containing 100 or 500 p.p.m. silymarin for 24 weeks. At week 34, feeding of 500 p.p.m. silymarin during the promotion phase significantly inhibited the incidence of tongue carcinoma, when compared with 4-NQO alone group (20% versus 64%, P = 0.019). Dietary silymarin decreased the cell proliferating activity and increased apoptotic index of tongue carcinoma. The treatment with silymarin decreased the polyamine content and prostaglandin (PG) E2 level in the tongue mucosa. Thus, the results indicate that feeding of silymarin (500 p.p.m.) during the promotion phase of 4-NQO-induced rat tumorigenesis exerts chemopreventive ability against tongue squamous cell carcinoma through modification of phase II enzymes activity, cell proliferation, and/or PGE2 content.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Miyamoto, Y. Yasui, M. Kim, S. Sugie, A. Murakami, R. Ishigamori-Suzuki, and T. Tanaka A novel rasH2 mouse carcinogenesis model that is highly susceptible to 4-NQO-induced tongue and esophageal carcinogenesis is useful for preclinical chemoprevention studies Carcinogenesis, February 1, 2008; 29(2): 418 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Deep and R. Agarwal Chemopreventive Efficacy of Silymarin in Skin and Prostate Cancer Integr Cancer Ther, June 1, 2007; 6(2): 130 - 145. [Abstract] [PDF]
|
|
|
|
|
|
H. Makita, M. Mutoh, T. Maruyama, K. Yonemoto, A. Kobayashi, H. Fujitsuka, M. Toida, T. Shibata, S. Miyamoto, Y. Yasui, et al. A prostaglandin E2 receptor subtype EP1-selective antagonist, ONO-8711, suppresses 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis Carcinogenesis, March 1, 2007; 28(3): 677 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Malewicz, Z. Wang, C. Jiang, J. Guo, M. P. Cleary, J. P. Grande, and J. Lu Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements Carcinogenesis, September 1, 2006; 27(9): 1739 - 1747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kohno, R. Suzuki, S. Sugie, H. Tsuda, and T. Tanaka Dietary Supplementation with Silymarin Inhibits 3,2'-Dimethyl-4-Aminobiphenyl-Induced Prostate Carcinogenesis in Male F344 Rats Clin. Cancer Res., July 1, 2005; 11(13): 4962 - 4967. [Abstract] [Full Text] [PDF]
|
|