NO INHIBITORY EFFECTS OF (−)-EPIGALLOCATECHIN GALLATE AND LYCOPENE ON SPONTANEOUS HEPATOTUMORIGENESIS IN C3H/HeN MICE

[Original Article]

NO INHIBITORY EFFECTS OF (−)-EPIGALLOCATECHIN GALLATE AND
LYCOPENE ON SPONTANEOUS HEPATOTUMORIGENESIS IN
C3H/HeN MICE

YOSHIHISA TAKAHASHI¹⁾, YUKIHIKO HARA²⁾, MASAYO IMANAKA³⁾,
HIDEKI WANIBUCHI³⁾, KIYOJI TANAKA⁴⁾, TAKATOSHI ISHIKAWA⁵⁾,
SHIGEO MORI¹⁾ and TOSHIO FUKUSATO¹⁾

¹⁾Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan, ²⁾Mitsui Norin Co., Ltd., Tokyo, Japan, ³⁾Department of Pathology, Osaka City University Medical School, Osaka, Japan, ⁴⁾Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University and Solution-Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Suita, Japan and ⁵⁾Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

(Received March 11, 2009, accepted March 3, 2010)

Abstract: Although several studies have indicated that (−)-epigallocatechin gallate (EGCG) and lycopene, representative dietary antioxidants, inhibit chemically induced animal tumorigenesis, only a few studies have examined the inhibitory effects of these compounds on spontaneous liver tumorigenesis in rodents. In this study, we investigated the inhibitory effects of these compounds on the formation of spontaneous liver tumors in C3H/HeN mice. We used xeroderma pigmentosum group A (XPA) gene-deficient mice to simultaneously examine whether the knockout mice could be used as a sensitive animal model. In addition, we examined the levels of 8-hydroxy-2?L-deoxyguanosine (8-OHdG)—a marker of reactive oxygen species-induced DNA injury—in liver tissue. Male XPA +/+, XPA +/−, and XPA −/− mice with a C3H/HeN genetic background were divided into 3 groups:control, EGCG, and lycopene. Autopsy at 18 months of age revealed that EGCG and lycopene did not exhibit obvious suppressive effects on the development of liver tumors in any XPA genotype;further, the XPA genotype did not influence any susceptibility to liver tumors. With regard to 8-OHdG levels in non-tumorous liver tissue at 8 months of age, EGCG showed no significant inhibitory effects and lycopene showed significant inhibitory effects only in XPA +/− mice. The present study demonstrates that contrary to previous reports of the inhibitory effects of EGCG and lycopene on the development of various carcinogen?@-induced animal tumors, these compounds exert no chemopreventive effects on spontaneous liver tumorigenesis in C3H/HeN mice. EGCG and lycopene may inhibit carcinogen-induced tumors through properties other than their antioxidant abilities.

Key words: (−)-Epigallocatechin gallate, Knockout mice, Lycopene, Spontaneous liver tumor, Xeroderma pigmentosum group A

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Corresponding author:Yoshihisa Takahashi, M.D.
E-mail:ytakaha-tky@umin.ac.jp
http://fmu.ac.jp/home/lib/F-igaku/
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