Journal of Food Hygiene and Safety (한국식품위생안전성학회지)

The Korean Society of Food Hygiene and Safety (한국식품위생안전성학회)
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Human Androgen Receptor-Mediated Endocrine Disrupting Potential of Parabens and Triclosan

파라벤류와 트리글로산의 인체 안드로겐 수용체 매개 내분비계 교란작용

  • Ji-Won Kim (Department of Food Safety and Regulatory Science, Chung-Ang University) ;
  • Hee-Seok, Lee (Department of Food Safety and Regulatory Science, Chung-Ang University)
  • 김지원 (중앙대학교 식품안전규제과학과) ;
  • 이희석 (중앙대학교 식품안전규제과학과)
  • Received : 2023.07.14
  • Accepted : 2023.10.12
  • Published : 2023.10.30
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Abstract

This study aimed to determine the human androgen receptor (AR)-mediated endocrine disrupting potential of parabens and triclosan in food and household products using a cell-based assay in the OECD TG No.458, the 22Rv1/MMTV_GR-KO transcriptional activation assay. Four parabens (methyl-, ethyl-, propyl-, and butyl-) are determined as AR antagonists in OECD TG No.458. However, their AR antagonistic effects were not exhibited in the presence of the S9 hepatic fraction. Triclosan is also classified as an AR antagonist, and the AR antagonistic effect induced by triclosan significantly decreased in the presence of the phase I + II S9 fraction. Regarding the mechanism of AR antagonism induced by parabens and triclosan, the AR-mediated endocrine disrupting effects were exhibited through suppressing the translocation of ligand-bound AR to the nucleus via blocking of AR dimerization in the cytosol. These results indicate that the four parabens and triclosan have AR-mediated endocrine disrupting potential through an AR antagonistic effect via inhibiting AR dimerization; however, their endocrine disrupting effects deceased in the presence of hepatic metabolic enzymes.

본 연구는 OECD TG No. 458, 22Rv1/MMTV_GR-KO 전사 활성화 분석법을 포함한 세포 기반 분석법을 사용하여 식품 및 생활용품에 포함된 파라벤과 트리클로산의 인간 안드로겐 수용체를 매개하는 내분비계 교란 가능성을 확인하는 것을 목표로 한다. 4가지 파라벤(메틸-, 에틸-, 프로필-, 부틸-)은 OECD TG No.458에서 AR 길항제로 확인된 반면, 파라벤의 AR 길항 효과는 S9 간 분획물이 있는 경우 나타나지 않았다. 트리클로산 역시 AR 길항제로 분류되었으며, 트리클로산에 의해 유도된 AR 길항 효과는 S9 간 분획물이 존재할 때 제 1상+2상 대사에서 유의하게 감소되었다. 파라벤과 트리클로산에 의해 유도되는 AR 길항 기전은 세포질 내 AR 이량화를 차단하여, 리간드 결합 AR이 핵으로의 전위를 억제함으로써 AR 매개 내분비 교란 효과를 나타냈다. 이러한 결과는 4가지 파라벤과 트리클로산이 AR 이량화 저해를 통한 AR 길항 효과를 나타내는 AR 매개 내분비 교란 가능성을 가지고 있으나, 간 대사 효소가 존재할 경우 내분비 교란 효과는 감소됨을 시사한다.

Keywords

Acknowledgement

This work was supported by a grant (21153MFDS605) from the Ministry of Food and Drug Safety.

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