Preprint Article Version 2 NOT YET PEER-REVIEWED

Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

  1. Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
  2. Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, Ministry of Health, Labour and Welfare, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
Version 1 : Received: 17 August 2016 / Approved: 17 August 2016 / Online: 17 August 2016 (11:57:56 CEST)
Version 2 : Received: 23 September 2016 / Approved: 26 September 2016 / Online: 26 September 2016 (09:25:39 CEST)

A peer-reviewed article of this Preprint also exists.

Kakehashi, A.; Yoshida, M.; Tago, Y.; Ishii, N.; Okuno, T.; Gi, M.; Wanibuchi, H. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats. Toxins 2016, 8, 275. Kakehashi, A.; Yoshida, M.; Tago, Y.; Ishii, N.; Okuno, T.; Gi, M.; Wanibuchi, H. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats. Toxins 2016, 8, 275.

Journal reference: Toxins 2016, 8, 275
DOI: 10.3390/toxins8110275

Abstract

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3% and, more pronouncedly, of 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

Subject Areas

Pueraria mirifica; mammary gland; uterus; carcinogenesis; estrogenic activity; Donryu rat

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