| Research Abstract |
We performed an in vivo long-term animal experiment in order to see a modifying potential of 4 - nonylphenol (4-NP), a possible endocrine disrupter, on prostate carcinogenesis when given soon after weaning. In addition to this - in vivo experiment, an in vitro experiment to clarify the effects of 4-NP on growth of human and rat prostate cancer cells was carried out. <Experiment 1> Three weeks old male F344 rats were given 4-NP at dietary dose levels of 25, 250, 2,000 ppm for 3 weeks and then treated with 3,2-Dimethyl-4-aminobiphenyl (DMAB), a prostate carcinogen, at a dose of 50 mg/kg s.c. biweekly for 20 weeks. The experiment was terminated 40 weeks after the last injection of DMAB and all surviving animals were autopsied for pathological analysis of prostate tumor development. There was no significant differences in body weights and any relative organ weights, including male sexual organs and muscli levator ani, among groups. Multiplicity of prostatic intraepitherial neoplasia (PEST) and carcinoma of the prostate and dysplasia of the seminal vesicles demonstrated that pretreatment with 4-NP did not modify prostate carcinogenesis. <Experiment 2> We analyzed the effect of 4-NP on cell growth in vitro with human prostate cancer cell lines, PC3, LNCaP and DU145. Another cell line PLS10, established in our laboratory from invasive rat prostate cancer was analyzed, too. As a positive control, 17β-estradiol significantly suppressed the cell growth activity of PC3 cells, and the upward tendency of LNCaP cell growth was also observed. However 4-NP did not alter cell growth of all the cell lines at dose levels of 10^<-6> - 10^<-9> In conclusion, our data showed that 4-NP have no estrogenic effects and no modifying influences, on prostate carcinogenesis.
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