@article {127, title = {Screening of House Dust from Chinese Homes for Chemicals with Liver X Receptors Binding Activities and Characterization of Atherosclerotic Activity Using an Macrophage Cell Line and Mice.}, journal = {Environ Health Perspect}, volume = {127}, year = {2019}, month = {2019 11}, pages = {117003}, abstract = {

BACKGROUND: Atherosclerotic cardiovascular disease has become the leading cause of death worldwide, and environmental pollutants are increasingly recognized as risk factors for atherosclerosis. Liver X receptors (LXRs) play a central role in atherosclerosis; however, LXR activity of organic pollutants and associated potential risk of atherosclerosis have not yet been characterized.

OBJECTIVES: This study aimed to explore whether LXR-antagonistic chemicals are present in indoor house dust and, if so, to characterize this activity in relation to changes in macrophages and cardiovascular disease indicators in an atherosclerosis mouse model.

METHODS: We used a -down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for - and -antagonist activity. A chemical identified in this manner was assessed for its ability to induce cholesterol efflux and foam cell formation in RAW264.7 macrophages, to down-regulate the expression of two LXR-dependent genes, and , and finally to induce atherosclerotic lesions using an mouse model.

RESULTS: We identified the flame retardants triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPP) in house dust samples and demonstrated their ability to antagonize LXRs. The potency of TPHP was similar to that of the LXR-antagonist SR9238. TPHP could also inhibit cholesterol efflux and promote foam cell formation in RAW264.7 macrophages and mouse peritoneal macrophages and significantly promoted atherosclerotic lesion formation in the mouse model.

CONCLUSIONS: We found LXR-antagonist chemicals in environmental samples of indoor dust from Chinese homes. One of the chemicals, TPHP, was able to promote the development of atherosclerotic lesions in the mouse model. These results highlight the need to assess the LXR-antagonist activities of pollutants in future environmental management programs. https://doi.org/10.1289/EHP5039.

}, keywords = {Air Pollutants, Air Pollution, Indoor, Animals, Atherosclerosis, China, Dust, Liver X Receptors, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, ApoE, RAW 264.7 Cells}, issn = {1552-9924}, doi = {10.1289/EHP5039}, author = {Hu, Wenxin and Jia, Yingting and Kang, Qiyue and Peng, Hui and Ma, Haojia and Zhang, Shiyi and Hiromori, Youhei and Kimura, Tomoki and Nakanishi, Tsuyoshi and Zheng, Lemin and Qiu, Yifu and Zhang, Zhaobin and Wan, Yi and Hu, Jianying} } @article {120, title = {Malformations of the endangered Chinese sturgeon, Acipenser sinensis, and its causal agent.}, journal = {Proc Natl Acad Sci U S A}, volume = {106}, year = {2009}, month = {2009 Jun 09}, pages = {9339-44}, abstract = {

The anadromous Chinese sturgeon (Acipenser sinensis) is endangered and listed among the first class of protected animals in China. The possible causes for the decline of this species are the effects of synthetic chemicals, and loss of critical habitat. Chinese sturgeon in the Yangtze River have accumulated triphenyltin (TPT) to 31-128 ng/g wet weigh (ww) in liver, which is greater than the concentrations of tributyltin (\<1.0 ng/g ww). Maternal transfer of TPT has resulted in concentrations of 25.5 +/- 13.0 ng/g ww in eggs of wild Chinese sturgeon, which poses a significant risk to the larvae naturally fertilized or hatched in the Yangtze River. The incidence of deformities in fry was 7.5\%, with 1.2\% of individuals exhibiting ocular abnormal development, and 6.3\% exhibited skeletal/morphological deformations. The incidences of both ocular and skeletal/morphological deformations were directly proportional to the TPT concentration in the eggs of both the Chinese sturgeon and the Siberian sturgeon (Acipenser baerii) in controlled laboratory studies. The rates of deformities in the controlled studies were consistent with the rates caused at the similar concentrations in eggs collected from the field. Thus, TPT is the causal agent to induce the malformation of larvae of Chinese sturgeon. The incidence of deformed larvae of Chinese sturgeon is an indicator of overall population-level effects of TPT on Chinese sturgeon, because TPT at environmentally relevant concentrations can result in significantly decrease both quality and quantity of eggs and spawning frequency of fish.

}, keywords = {Animals, China, Fishes, Organotin Compounds, Trialkyltin Compounds, Water Pollutants, Chemical}, issn = {1091-6490}, doi = {10.1073/pnas.0809434106}, author = {Hu, Jianying and Zhang, Zhaobin and Wei, Qiwei and Zhen, Huajun and Zhao, Yanbin and Peng, Hui and Wan, Yi and Giesy, John P and Li, Luoxin and Zhang, Bo} }