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Low-dose bisphenol A increases bile duct proliferation in juvenile rats: A possible evidence for risk of liver cancer in the exposed population?

Title
Low-dose bisphenol A increases bile duct proliferation in juvenile rats: A possible evidence for risk of liver cancer in the exposed population?
Authors
Jeong J.S.Nam K.T.Lee B.Pamungkas A.D.Song D.Kim M.Yu W.-J.Lee J.Jee S.Park Y.H.Lim K.-M.
Ewha Authors
임경민
SCOPUS Author ID
임경민scopus
Issue Date
2017
Journal Title
Biomolecules and Therapeutics
ISSN
1976-9148JCR Link
Citation
vol. 25, no. 5, pp. 545 - 552
Keywords
Bile duct proliferationBisphenol AJuvenile animalsToxicokinetics
Publisher
Korean Society of Applied Pharmacology
Indexed
SCIE; SCOPUS; KCI WOS scopus
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 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. © 2017 The Korean Society of Applied Pharmacology.
DOI
10.4062/biomolther.2017.148
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약학대학 > 약학과 > Journal papers
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