Modifying effects of a possible endocrine disrupting chemical on rat prostate carcinogenesis

我们进行了一项活体长期动物实验，以观察4-壬基酚(4-NP)--一种可能的内分泌干扰物--在断奶后不久给予前列腺癌的修饰潜力。除了体内实验外，还进行了4-NP对人和大鼠前列腺癌细胞生长的影响的体外实验。实验1：3周龄雄性F344大鼠以25、250、2000ppm的4-NP灌胃3周后，皮下注射前列腺癌致癌物3，2-二甲基-4-氨基联苯(DMAB)，剂量为50 mg/kg。每两周一次，为期20周。实验在最后一次注射DMAB后40周终止，所有存活的动物都进行了身体解剖，以进行前列腺癌的病理分析。体重和任何相关器官重量，包括男性性器官和提肛肌，在组间没有显著差异。前列腺上皮内瘤变(PEST)、前列腺癌和精囊异型增生的多发性表明，4-NP预处理不能改变前列腺癌的发生。实验2分析了4-NP对人前列腺癌PC3、LNCaP和DU145细胞体外生长的影响。对我们实验室建立的另一株侵袭性大鼠前列腺癌细胞系PLS10也进行了分析。作为阳性对照，17β-雌二醇显著抑制PC3细胞的生长活性，并呈上升趋势。然而，4-NP在10^~(-6)~(-6)~(-9)的剂量水平下对所有细胞系的细胞生长均无明显影响。

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.