Developing in vitro reporter gene assays to assess the hormone receptor activities of chemicals frequently detected in drinking water.
The present study intended to develop receptor-mediated luciferase reporter gene assays to evaluate and compare the estrogen receptor (ER), androgen receptor (AR) and thyroid hormone receptor (TR) activities of target chemicals. Di-2-ethylhexyl-phthalate (DEHP), chlorpyrifos (CPF), 2,4-dichlorophenoxyacetic acid (2,4-D) and bisphenol A (BPA) are some of the most common contaminants in drinking water and are frequently detected in China and worldwide. The chemicals were tested at concentrations of 0.1, 1, 10 and 100 times their maximum contaminant level in drinking water. The results showed that BPA possessed various activities on ER, AR and TR. DEHP and CPF could suppress 17β-estradiol or testosterone activity with different potencies, and DEHP possessed weaker anti-thyroid hormone activity. 2,4-D showed no agonist or antagonist activity against these hormone receptors, but it significantly enhanced the activity of testosterone through AR. Furthermore, the mixture of DEHP and CPF exhibited stronger ER and AR antagonist activities than each single component alone, but their combined effects were less than the expected effects based on the additive model. These results implied that the transcription activation mediated by hormone receptors was the potential endocrine-disrupting mechanism of the test chemicals. Our study also provided useful tools for evaluation of their endocrine disrupting activity.
Jiangsu Provincial Centre for Disease Prevention and Control, Nanjing 210009, China. njmu_sunhong@hotmail.com
Hong
H
Sun
Chaozong
C
Si
Qian
Q
Bian
Xiaodong
X
Chen
Liansheng
L
Chen
Xinru
X
Wang
D015084:2,4-Dichlorophenoxyacetic Acid / Q000032:analysis / Q000633:toxicity; D000818:Animals; D001559:Benzhydryl Compounds; D002681:China; D002522:Chlorocebus aethiops; D004390:Chlorpyrifos / Q000032:analysis / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000032:analysis / Q000633:toxicity; D060766:Drinking Water / Q000032:analysis / Q000737:chemistry*; D052244:Endocrine Disruptors / Q000633:toxicity; D004958:Estradiol / Q000235:genetics; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000032:analysis / Q000633:toxicity; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D015084:2,4-Dichlorophenoxyacetic Acid; D001559:Benzhydryl Compounds; D004390:Chlorpyrifos; D004051:Diethylhexyl Phthalate; D060766:Drinking Water; D052244:Endocrine Disruptors; D004958:Estradiol; D008156:Luciferases; D010636:Phenols; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D013739:Testosterone; D014874:Water Pollutants, Chemical; C410798:AR protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds