TY - JOUR
T1 - Liquid chromatography-mass spectrometry-based metabolomics and lipidomics reveal toxicological mechanisms of bisphenol F in breast cancer xenografts
AU - Zhao, Chao
AU - Xie, Peisi
AU - Wang, Hailin
AU - Cai, Zongwei
N1 - Funding Information:
The work was supported by grants from the National Natural Science Foundation of China (21507106, 21505111, 91543202), Hong Kong Baptist University Strategic Development Fund (15-1012-P04), General Research Fund (12301915 and 12319716) and Collaborative Research Fund (C2014-14E) from Research Grants Council of Hong Kong.
Funding Information:
The work was supported by grants from the National Natural Science Foundation of China ( 21507106 , 21505111 , 91543202 ), Hong Kong Baptist University Strategic Development Fund ( 15-1012-P04 ), General Research Fund ( 12301915 and 12319716 ) and Collaborative Research Fund ( C2014-14E ) from Research Grants Council of Hong Kong .
PY - 2018/9/15
Y1 - 2018/9/15
N2 - Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts. Our results demonstrated that BPF exposure disturbed the metabolome and lipidome of liver and kidney. Exposure induced reprogramming of the glutathione (GSH) biosynthesis and glycolytic metabolism by activating glycine, serine, cysteine, glutamine, lactate and pyruvate in liver and kidney tissues. It also perturbed the biosynthesis and degradation of glycerophospholipids (GPs) and glycerolipids (GLs), resulting in abnormality of membrane homeostasis and cellular functions in kidney tissues. Moreover, spatial distribution and profile of metabolites changed across renal cortex and medulla regions after BPF treatment. Levels of phosphatidylethanolamines (PE) and triacylglycerols (TAG) increased in renal medulla and pelvis, while the levels of phosphatidylcholines (PC) and phosphatidylinositols (PI) increased in cortex and pelvis. These observations offer a deeper understanding of critical role of metabolites and lipid reprogramming in BPF-induced biological effects.
AB - Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts. Our results demonstrated that BPF exposure disturbed the metabolome and lipidome of liver and kidney. Exposure induced reprogramming of the glutathione (GSH) biosynthesis and glycolytic metabolism by activating glycine, serine, cysteine, glutamine, lactate and pyruvate in liver and kidney tissues. It also perturbed the biosynthesis and degradation of glycerophospholipids (GPs) and glycerolipids (GLs), resulting in abnormality of membrane homeostasis and cellular functions in kidney tissues. Moreover, spatial distribution and profile of metabolites changed across renal cortex and medulla regions after BPF treatment. Levels of phosphatidylethanolamines (PE) and triacylglycerols (TAG) increased in renal medulla and pelvis, while the levels of phosphatidylcholines (PC) and phosphatidylinositols (PI) increased in cortex and pelvis. These observations offer a deeper understanding of critical role of metabolites and lipid reprogramming in BPF-induced biological effects.
KW - Bisphenol F
KW - Breast cancer xenografts
KW - LC–MS/MS
KW - MALDI-MSI
KW - Metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85047207541&partnerID=8YFLogxK
U2 - 10.1016/j.jhazmat.2018.05.010
DO - 10.1016/j.jhazmat.2018.05.010
M3 - Journal article
C2 - 29759594
AN - SCOPUS:85047207541
SN - 0304-3894
VL - 358
SP - 503
EP - 507
JO - Journal of Hazardous Materials
JF - Journal of Hazardous Materials
ER -