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ORIGINAL RESEARCH ARTICLE

Chemopreventive Effects of Hydroxymatairesinol on Uterine Carcinogenesis in Donryu Rats

Shin-Ichi Katsuda^1,*, Midori Yoshida, Niina Saarinen, Annika Smeds, Dai Nakae, Risto Santti and Akihiko Maekawa

^* Department of Biological Safety Research, Japan Food Research Laboratories, Tama-shi, Tokyo 206-0025, Japan; Department of Pathology, Sasaki Institute, Chiyoda-ku, Tokyo 101-0062, Japan; Department of Anatomy, Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland; and Department of Organic Chemistry, Å bo Akademi University, Biskopsgatan 8, FIN-20500 Turku, Finland

To whom requests for reprints should be addressed at ¹ Department of Biological Safety Research, Japan Food Research Laboratories, 6-11-10 Nagayama, Tama-shi, Tokyo 206-0025, Japan. E-mail: katudas{at}jfrl.or.jp

Hydroxymatairesinol (HMR), obtained from the heartwood of spruce (Picea abies), has been demonstrated to exert chemo-preventive effects on the development of mammary tumors in rats. To examine the influence of HMR on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at 11 weeks of age and fed thereafter 0, 200, or 600 ppm HMR mixed in the soy-containing diet until 15 months of age. Incidences of uterine adenocarcinoma in both 200 and 600 ppm HMR-dosed groups were significantly reduced to 11% and 15%, respectively, less than 50% of 0 ppm, at the end of the experiment (P < 0.05). A delay in the start of persistent estrus by HMR was observed at 8 months of age compared with controls given carcinogen alone. From urinalysis, HMR was metabolized mainly to enterolactone and hydroxyenterolactone. These findings suggest that HMR or its metabolites exert chemo-preventive effects in the rat ENNG-uterine carcinogenesis model.

Key Words: hydroxymatairesinol • rat • endometrial adenocarcinoma • chemoprevention

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