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http://dx.doi.org/10.4062/biomolther.2017.148

Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?  

Jeong, Ji Seong (Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology)
Nam, Ki Taek (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine)
Lee, Buhyun (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine)
Pamungkas, Aryo Dimas (College of Pharmacy, Korea University)
Song, Daeun (College of Pharmacy, Ewha Womans University)
Kim, Minjeong (College of Pharmacy, Ewha Womans University)
Yu, Wook-Joon (Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology)
Lee, Jinsoo (Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology)
Jee, Sunha (Department of Epidemiology and Health Promotion, and Institute for Health Promotion, Graduate School of Public Health, Yonsei University)
Park, Youngja H. (College of Pharmacy, Korea University)
Lim, Kyung-Min (College of Pharmacy, Ewha Womans University)
Publication Information
Biomolecules & Therapeutics / v.25, no.5, 2017 , pp. 545-552 More about this Journal
Abstract
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 $C_{max}$, 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 $C_{max}$ 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.
Keywords
Bisphenol A; Toxicokinetics; Bile duct proliferation; Juvenile animals;
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