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Modifying Effects of 1'-Acetoxychavicol Acetate (ACA) and the Novel Synthetic Retinoids Re-80, Am-580 and Am-55P in a Two-Stage Carcinogenesis Model in Female Rats

Department of Experimental Pathology and Tumor Biology, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Masao Hirose

Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan, m-hirose{at}nihs.go.jp

Satoru Takahashi

Department of Experimental Pathology and Tumor Biology, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Katsumi Imaida

Onco-Pathology, Department of Pathology and Host-Defense, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan

Nobuyuki Ito

Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Koichi Shudo

Research Foundation Itsuu Laboratory, 2-28-10, Tamagawa, Setagaya-Ku, Tokyo 158-0094, Japan

Hajime Ohigashi

Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Oikawa-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan, and

Akira Murakami

Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita-cho, Naka-gun, Wakayama 649-6493, Japan

Tomoyuki Shirai

Department of Experimental Pathology and Tumor Biology, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Effects of dietary administration of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (Re-80); 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]nicotinic acid (Am-55P) were examined using a two-stage rat carcinogenesis model. A total of 190 female SD rats was treated sequentially with 1,2-dimethylhydrazine (DMH, s.c.); 7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, in the drinking water) during the first three weeks (DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated Re-80 (at dose levels of 1.0 or 0.4 ppm), Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm), all-trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After DDD-initiation, all-trans-retinoic acid at the high dose delayed the development of mammary tumors. The multiplicity of colon tumors in the group fed Am-55P and the incidences of nephroblastomas with ACA or Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on tumor development in any organs. Thus, among ACA and the novel synthetic retinoids tested, only Am-55P showed a weak inhibitory effect on a neoplasm of general interest under the present experimental conditions.

Key Words: Synthetic retinoids • 1'-acetoxychavicol acetate • chemoprevention • rat • Re-80 • Am-580 • Am-55P.

Toxicologic Pathology, Vol. 32, No. 2, 250-257 (2004)
DOI: 10.1080/01926230490274425


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