title: Predicting cytotoxicity of complex mixtures in high cancer incidence regions of the Huai River Basin based on GC-MS spectrum with partial least squares regression.
abstract: Complex mixture exposures, such as those associated with water sources, are an important issue in health risk assessment. This study assessed the cytotoxicity of chemical mixtures extracted from water sources in regions of the Huai River Basin with high cancer incidences and built statistical models of cytotoxicity based on pollution profiles that were measured with gas chromatography-mass spectrometry (GC-MS). Both surface and ground waters were collected from rural water sources of Shenqiu County, Henan Province of China from 2008 to 2011 and extracted with XAD-2 resigns. Cytotoxicity was evaluated with Chinese hamster ovary K1 (CHO-K1) cells and compared against the pollution profiles of the extracts. IC50 of water samples ranged from 0.023 to 0.338L-eq/mL. The pollutants in waters determined by GC-MS are complex and some of the compounds that contributed to cytotoxicity lack toxicity data. A partial least squares (PLS) regression model of cytotoxicity was built based on linear aggregation of predictor variables (i.e., peaks for single compounds in the gas chromatograms). The PLS model contains 2 PLS factors extracted from 141 variables. The model was validated internally with training data permutation and externally with a test sample. The model explained 92% of the cytotoxicity in the training samples and 40% in the test sample. This approach provides a general, rapid method for relating water toxicity to GC-MS chromatograms and for predicting the compounds that contribute most to toxicity.
authors.affiliation: Key Laboratory of Public Health and Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, Yi Xue Yuan Road 138, Shanghai 200032, China.
authors.forename: Dajun
authors.initials: D
authors.lastname: Tian
authors.affiliation: Key Laboratory of Public Health and Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, Yi Xue Yuan Road 138, Shanghai 200032, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Key Laboratory of the Public Health Safety, Ministry of Education, Department of Nutrition and Food Hygiene, Fudan University, Shanghai 200032, China.
authors.forename: Gengsheng
authors.initials: G
authors.lastname: He
authors.affiliation: Chinese Center for Disease Control and Prevention, Nan Wei Road 29, Beijing 100050, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.affiliation: Key Laboratory of the Public Health Safety, Ministry of Education, Department of Childhood and Adolescent, Fudan University, Shanghai 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tan
authors.affiliation: Key Laboratory of Public Health and Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, Yi Xue Yuan Road 138, Shanghai 200032, China. Electronic address: htan@fudan.edu.cn.
authors.forename: Weidong
authors.initials: W
authors.lastname: Qu
mesh_terms: D000818:Animals; D016466:CHO Cells; D002681:China; D045424:Complex Mixtures / Q000032:analysis / Q000633:toxicity*; D006224:Cricetinae; D003412:Cricetulus; D004784:Environmental Monitoring; D008401:Gas Chromatography-Mass Spectrometry; D060587:Groundwater / Q000032:analysis*; D016018:Least-Squares Analysis; D045483:Rivers / Q000737:chemistry*; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*
chemical_list: D045424:Complex Mixtures; D014874:Water Pollutants, Chemical
keywords: Cytotoxicity; Mixture toxicology; Partial least squares; Regression; Water