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Carcinogenesis Advance Access published online on December 7, 2005
Carcinogenesis, doi:10.1093/carcin/bgi277
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received April 13, 2005
Revised November 15, 2005
Accepted November 20, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

N-Acetylcysteine and S-methylcysteine inhibit MeIQx rat hepatocarcinogenesis in the post-initiation stage

Motome Nishikawa-Ogawa 1, Hideki Wanibuchi 1, Keiichirou Morimura 1, Anna Kinoshita 1, Takayuki Nishikawa 1, Shuji Hayashi 1, Yoshihisa Yano 2, and Shoji Fukushima 1 *

1 Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
2 Department of Biochemistry, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

* To whom correspondence should be addressed.
Shoji Fukushima, E-mail: fukuchan{at}med.osaka-cu.ac.jp


  Abstract

N-Acetylcysteine (NAC) and S-methylcysteine (SMC), water soluble organosulfur compounds contained in garlic, were evaluated for chemoprevention of hepatocarcinogenesis after 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) initiation in rats. Intergastric treatment with NAC or SMC five times a week resulted in decreased numbers and areas of preneoplastic, glutathione S-transferase placental form (GST-P) positive foci of the liver in a dose-dependent manner. Moreover, cell proliferation was reduced in GST-P positive foci by NAC and SMC. Insulin-like growth factor-I (IGF-I) and nitric oxide synthase (iNOS) mRNA expressions were found down-regulated in the liver by NAC. The studies indicate that NAC can serve as chemopreventive agent for rat hepatocarcinogenesis induced by MeIQx by reducing cell-proliferation, which may involve IGF-I and iNOS down-regulation.


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