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

Ji Seong Jeong, KiTaek Nam, Buhyun Lee, Aryo Dimas Pamungkas, Daeun Song, Minjeong Kim, Wook Joon Yu, Jinsoo Lee, Sunha Jee, Youngja H. Park, Kyung Min Lim

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Pages (from-to)545-552
Number of pages8
JournalBiomolecules and Therapeutics
Volume25
Issue number5
DOIs
Publication statusPublished - 2017 Sep 1

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Liver Neoplasms
Bile Ducts
Liver
Ducts
Rats
Population
Area Under Curve
Sexual Maturation
Xenobiotics
Human Mammary Glands
Analysis of variance (ANOVA)
Sprague Dawley Rats
Toxicity
bisphenol A
Neoplasms
Analysis of Variance
Age Groups
Eating
Body Weight
Inflammation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Jeong, Ji Seong ; Nam, KiTaek ; Lee, Buhyun ; Pamungkas, Aryo Dimas ; Song, Daeun ; Kim, Minjeong ; Yu, Wook Joon ; Lee, Jinsoo ; Jee, Sunha ; Park, Youngja H. ; Lim, Kyung Min. / Low-dose bisphenol A increases bile duct proliferation in juvenile rats : A possible evidence for risk of liver cancer in the exposed population?. In: Biomolecules and Therapeutics. 2017 ; Vol. 25, No. 5. pp. 545-552.
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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 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.",
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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; Nam, KiTaek; Lee, Buhyun; Pamungkas, Aryo Dimas; Song, Daeun; Kim, Minjeong; Yu, Wook Joon; Lee, Jinsoo; Jee, Sunha; Park, Youngja H.; Lim, Kyung Min.

In: Biomolecules and Therapeutics, Vol. 25, No. 5, 01.09.2017, p. 545-552.

Research output: Contribution to journalArticle

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T2 - A possible evidence for risk of liver cancer in the exposed population?

AU - Jeong, Ji Seong

AU - Nam, KiTaek

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

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