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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?
- Low-dose bisphenol A increases bile duct proliferation in juvenile rats: A possible evidence for risk of liver cancer in the exposed population?
- 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
- SCOPUS Author ID
- Issue Date
- Journal Title
- Biomolecules and Therapeutics
- vol. 25, no. 5, pp. 545 - 552
- Bile duct proliferation; Bisphenol A; Juvenile animals; Toxicokinetics
- Korean Society of Applied Pharmacology
- SCIE; SCOPUS; KCI
- 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.
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