Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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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?

  • 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)
  • Received : 2017.07.20
  • Accepted : 2017.08.03
  • Published : 2017.09.01
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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

References

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