TY - JOUR
T1 - Low-dose bisphenol A increases bile duct proliferation in juvenile rats
T2 - A possible evidence for risk of liver cancer in the exposed population?
AU - Jeong, Ji Seong
AU - Nam, Ki Taek
AU - Lee, Buhyun
AU - Pamungkas, Aryo Dimas
AU - Song, Daeun
AU - Kim, Minjeong
AU - Yu, Wook Joon
AU - Lee, Jinsoo
AU - Jee, Sunha
AU - Park, Youngja H.
AU - Lim, Kyung Min
N1 - Funding Information:
This research was supported by grants from Ministry of Food and Drug Safety in 2015 (15162MFDS631) and the Korea Mouse Phenotyping Center (2016M3A9D5A01952416).
Publisher Copyright:
© 2017 The Korean Society of Applied Pharmacology.
PY - 2017/9
Y1 - 2017/9
N2 - Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in Cmax, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in Cmax and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.
AB - Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in Cmax, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in Cmax and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.
KW - Bile duct proliferation
KW - Bisphenol A
KW - Juvenile animals
KW - Toxicokinetics
UR - http://www.scopus.com/inward/record.url?scp=85029152393&partnerID=8YFLogxK
U2 - 10.4062/biomolther.2017.148
DO - 10.4062/biomolther.2017.148
M3 - Article
AN - SCOPUS:85029152393
SN - 1976-9148
VL - 25
SP - 545
EP - 552
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
IS - 5
ER -