Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?.
10.4062/biomolther.2017.148
- Author:
Ji Seong JEONG
1
;
Ki Taek NAM
;
Buhyun LEE
;
Aryo Dimas PAMUNGKAS
;
Daeun SONG
;
Minjeong KIM
;
Wook Joon YU
;
Jinsoo LEE
;
Sunha JEE
;
Youngja H PARK
;
Kyung Min LIM
Author Information
1. Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Bisphenol A;
Toxicokinetics;
Bile duct proliferation;
Juvenile animals
- MeSH:
Animals;
Area Under Curve;
Bile Ducts*;
Bile*;
Body Weight;
Child;
Female;
Humans;
Inflammation;
Liver Neoplasms*;
Liver*;
Male;
Mammary Glands, Human;
Rats*;
Rats, Sprague-Dawley;
Toxicokinetics;
Xenobiotics
- From:Biomolecules & Therapeutics
2017;25(5):545-552
- CountryRepublic of Korea
- Language:English
-
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.
