| Research Abstract |
We tried to establish in vivo bioassy system to identify any possible chemopreventive compounds on rat prostate carcinogenesis, since the mortality rate of prostate cancer is gradually increasing in Japan like western countries especially United States. Animal models are essential to identify chemopreventors on prostate carcinogenesis. However, conventional rat prostate models, which are used N-hydroxy-3,2'-dimethyl-4-aminobiphenyl (DMAB) or 2-amino-1-methyl-6-phenylimidazo-[4,5-b] pyridine (PhIP) as rat prostate carcinogens, require nearly 60 weeks for experimental duration. It is apparently too long to use as a bioassy models for detecting chemopreventors. We recently introduced transgenic rats with SV40T antigen under probasin promoter control, allowing prostate-specific gene expression. All of animals of these male rats have prostate adenocarcinomas by 15 weeks old, without any carcinogen treatment. Therefore, this transgenic rats can be used as an medium-term bioassy models for ra
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t prostate carcinogenesis, including for detecting chemopreventors on prostate carcinogenesis.
[Materials and Methods]
Six-week-old 45 male transgenic rats were divided into 3 groups, containing 15 animals for each group. Lycopene and quercetin were selected possible chemopreventive compounds, since these chemicals have been reported as chemopreventors on prostate carcinogenesis in animal models. Animals in Group 1 were given lycopene at 45ppm in their powder basal diet, animals in Group 2 were given quercetin at 2% in their diet, and those in Group 3 were given only basal power diet and treated as control group. All of animals were sacrificed at week 15. Any clinical parameters, including growth curve and food consumptions, were not different among groups. At the autopsy, body weights, liver and kidney weights were not different between groups. Serum testosterone levels were 9.9-1.2ng/ml, and there were not statistically different groups. Prostate lesions were classified as prostatic intra-epithelial neoplasia (PIN) and adenocarcinoma based on pathological evaluation. Prostate were divided into ventral, dorsal, lateral and anterior lobes, and each lesions were evaluation in each lobes. All of animals in any group have PIN and adenocarcinomas in all lobes of prostate. Most of all adenocarcinomas were diagnosed as invasive carcinomas, but 4 out 15 in Group 1, and 1 out of 14 in Groups 2 and 3. Although some tendency of cancer preventive effect in lycopene treated group was observed, there were not statistically different between groups. These results indicate that this transgenic animal model is not suitable animals models for detecting chemopreventors on prostate carcinogenesis. Less
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