Preventive effects of fermented brown rice and rice bran against N‑nitrosobis (2‑oxopropyl) amine‑induced pancreatic tumorigenesis in male hamsters

Kuno,Toshiya; Takahashi,Satoru; Tomita,Hiroyuki; Hisamatsu,Kenji; Hara,Akira; Hirata,Akihiro; Kobayashi,Hiroshi; Mori,Hideki

doi:10.3892/ol.2015.3809

Preventive effects of fermented brown rice and rice bran against N‑nitrosobis (2‑oxopropyl) amine‑induced pancreatic tumorigenesis in male hamsters

Authors:
- Toshiya Kuno
- Satoru Takahashi
- Hiroyuki Tomita
- Kenji Hisamatsu
- Akira Hara
- Akihiro Hirata
- Hiroshi Kobayashi
- Hideki Mori
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Affiliations: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Division of Animal Experiment, Life Science Research Center, Gifu University, Gifu 501‑1193, Japan, Sapporo Cancer Seminar, Chuo‑ku, Sapporo 064‑0820, Japan
Published online on: October 16, 2015 https://doi.org/10.3892/ol.2015.3809
Pages: 3377-3384
Copyright: © Kuno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fermented brown rice by Aspergillus oryzae (FBRA) is known to have the potential to prevent chemical carcinogenesis of the colon, liver, esophagus, urinary bladder, stomach and lungs in rodents. The present study examined the possible chemopreventive effects of FBRA on N‑nitrosobis(2‑oxopropyl)amine (BOP)‑induced pancreatic tumorigenesis in hamsters. Five‑week‑old male Syrian golden hamsters were divided into seven groups. Groups 1‑5 were subcutaneously injected with BOP (10 mg/kg body weight) four times during week 6 to induce pancreatic tumors, while groups 6 and 7 were injected with saline. Groups 2 and 3 were fed diets containing 5 and 10% FBRA, respectively, during the initiation phase. By contrast, groups 4 and 5 were fed diets containing 5 and 10% FBRA, respectively, during the post‑initiation phase. Group 6 received a diet containing 10% FBRA throughout the experiment, and group 7 was kept on the basal diet alone and served as the untreated control. At the termination of the study (week 22), oral intake of 10% FBRA (group 5) during the post‑initiation phase was identified to have significantly reduced the multiplicity (number of lesions/animal) of ductal adenocarcinoma [pancreatic intraepithelial neoplasia 3 (PanIN3); carcinoma in situ and invasive carcinoma] in comparison with group 1 control hamsters (0.24±0.44 vs. 0.71±0.72; P<0.05). Treatment with 10% FBRA in the post‑initiation phase inhibited the progression of normal/precancerous lesions (PanIN1, mild hyperplastic lesions; and PanIN2, papillary hyperplasia) to ductal adenocarcinomas. Furthermore, dietary exposure to 10% FBRA during the initiation (group 3) and post‑initiation phases (group 5) significantly reduced the multiplicity of PanIN2 (group 3, 0.55±0.69; group 5, 0.45±0.69; versus group 1, 1.26±1.24; P<0.05 and P<0.01, respectively). A significant reduction of Ki‑67 positivity of PanIN2 in group 5 was also confirmed (group 5, 0.05±0.03; group 1, 0.22±0.12; P<0.01). Using terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling, augmentation of apoptosis by FBRA exposure in the non‑lesional ductal epithelium and proliferative lesions was not evident. These findings indicate that FBRA exhibits inhibitory effects on BOP‑induced pancreatic tumorigenesis in hamsters due to the reduced proliferation rate of tumor cells. Thus, FBRA may be a promising chemopreventive agent in human pancreatic cancer.

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