Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development

Abstract

Background: High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics. Methods: Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, n = 15) and VC exposure-matched controls (n = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed. Results: Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling. Conclusions: The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.

A Metabolomics-Based Screening Proposal for Colorectal Cancer

“…The reduced concentration of 4-hydroxybenzyl alcohol reported herein has an established correlation in CRC metabolomics-based studies [40,45]. This metabolite shows good angiogenetic antagonist activity [46] and was decreased in polyvinyl chloride workers with hepatic hemangiosarcoma [47]. 4-hydroxybenzyl alcohol, (aka gastrodigenin), is an intermediate metabolite produced during the biosynthesis of thiamine by Escherichia coli.…”

Improvements in protective measures in factories with acetylene hydrochlorination and ethylene oxychlorination techniques declined risk assessment levels and affected liver health status

“…Both of them predominantly affected liver enzymes, forming 2-chloroethylene oxide, monochloroacetic acid, and the conjugated metabolic product of thiodiglycolic (thiodiacetic) acid (TDAA), which tend to be mutagenic and carcinogenic ( 10 ). Particularly, workers from the VCM division were subjected to simultaneous intensive exposure to concentrations of VCM ranging from 2.0 to 14.6 mg·m −3 and of 1,2-DCE from 15.0 to 87.2 mg·m −3 , while those from the PVC division were only exposed to concentrations of VCM ranging from 1.1 to 10.7 mg·m −3 ( 11 ). In addition to VCM, PVC was classified as a possible carcinogen (class 3) by the IARC.…”