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

可能的内分泌干扰化学物质对大鼠前列腺癌发生的影响

• 批准号: 11670223
• 负责人: SHIRAI Tomoyuki
• 金额: $ 2.37万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670223/
• 关键词: endocrine disruptor; 4-nonylphenol; prostate carcinogenesis; DMAB; rat; prostate; prostatic intraepithelial neoplasia; prostate cancer cell line; 前立線癌細胞株; ノニフェノール; ラット; 前立腺癌; 3,2'-dimethyl-4-aminobiphenyl; テストステロン; 幼若令; ノニルフェノール; 3,2'-dime

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.

我们进行了一项体内长期动物实验，目的是观察断奶后不久给予 4-壬基酚 (4-NP)（一种可能的内分泌干扰物）对前列腺癌发生的改变潜力。除了体内实验之外，还进行了一项体外实验来阐明 4-NP 对人和大鼠前列腺癌细胞生长的影响。 <实验1> 将3周龄的雄性F344大鼠以25、250、2,000ppm的饮食剂量水平给予4-NP 3周，然后以50mg/kg的剂量皮下注射前列腺致癌物3,2-二甲基-4-氨基联苯(DMAB)。每两周一次，持续 20 周。最后一次注射 DMAB 后 40 周终止实验，并对所有存活的动物进行尸检以进行前列腺肿瘤发展的病理分析。各组之间的体重和任何相对器官重量（包括男性性器官和提肛肌）没有显着差异。多种前列腺上皮内瘤变 (PEST) 和前列腺癌以及精囊发育不良表明，4-NP 预处理不会改变前列腺癌发生。 <实验2> 我们用人前列腺癌细胞系PC3、LNCaP和DU145在体外分析了4-NP对细胞生长的影响。我们还对我们实验室从侵袭性大鼠前列腺癌中建立的另一种细胞系 PLS10 进行了分析。作为阳性对照，17β-雌二醇显着抑制PC3细胞的细胞生长活性，并且也观察到LNCaP细胞生长呈上升趋势。然而，在10 ^ -6 - 10 ^ -9 的剂量水平下4-NP并没有改变所有细胞系的细胞生长。 总之，我们的数据表明4-NP对前列腺癌发生没有雌激素作用并且没有改变影响。

项目成果

Imaida K., Shirai T. et al.: "Organ dependent enhancement of rat 3,2'-dimethyl-4-aminobiphenyl (DMAB) carcinogenesis by 2-amino-l-methyl-6-phenylimidazo [4,5-6] pyridine (PhIP) : positive effects on the intestine but not the prostate"Carcinogenesis. 22. 1

Imaida K.、Shirai T. 等人：“2-氨基-1-甲基-6-苯基咪唑对大鼠 3,2-二甲基-4-氨基联苯 (DMAB) 致癌作用的器官依赖性增强 [4,5-6]

Moni, T., Shirai, T., et al.: "Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis"Jpn. J. Cancer Res.. 92. 1026-1033 (2001)

Moni, T.、Shirai, T. 等人：“番茄红素和姜黄素对实验性大鼠前列腺癌发生缺乏化学预防作用”Jpn。

Mori, T., Shirai., T et al.: "Beef tallow, but not perilla or corn oil, promotion of rat prostate and intestinal carcinogenesis by 3,2'-dimethyl-4-aminobiphenyl"Jpn. J. Cancer Res.. 92. 1026-1033 (2001)

Mori, T., Shirai., T 等人：“牛油，但不是紫苏油或玉米油，通过 3,2-二甲基-4-氨基联苯促进大鼠前列腺和肠癌发生”Jpn.

Ogawa,K.,Kimoto,N.,Asamoto,M.,Nakanishi,M.,Takahashi,S.,Shirai,T.: "Aberrant expression of p^<27kipl> is associated with malignant transformation of the rat urinary bladder epithelium"Carcinogenesis. 21. 117-121 (2000)

Okawa,K.、Kimoto,N.、Asamoto,M.、Nakanishi,M.、Takahashi,S.、Shirai,T.：“p^<27kipl> 的异常表达与大鼠膀胱上皮的恶性转化有关

Asamoto,M.,Ochiya,T.,Baba Toriyama,H.,Ota,T.,Sekiya,T.,Terada,M.,Tsudsa,H..: "Transgenic rats carrying human c-Ha-ras proto-oncogenes are highly susceptible to N-methyl-N-nitrosoures mammary carcinogenesis"Carcinogenesis. in press. (2000)

Asamoto,M.,Ochiya,T.,Baba Toriyama,H.,Ota,T.,Sekiya,T.,Terada,M.,Tsudsa,H..：“携带人类 c-Ha-ras 原癌基因的转基因大鼠