Abstract
ObjectiveThe aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting.MethodsWorkers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure.ResultsExpression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1β, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis.ConclusionThe pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure.
Highlights
Styrene is a volatile organic compound used in factories for synthesis of plastic products
To determine the genes differently expressed in styrene-exposed subjects compared with the nonexposed group, we used a customized PathwayFinder PCR Array with 84 human genes that are known to play a role in toxicology
Occupational exposure to styrene has steadily declined over the years due to improved industrial hygiene and more stringent regulations, the number of workers exposed to styrene is still high
Summary
Styrene is a volatile organic compound used in factories for synthesis of plastic products. Long-term chemical carcinogenesis bioassays showed that styrene caused lung cancers in several strains of mice and mammary cancers in rats and styrene-7,8-oxide caused tumors of the forestomach in rats and mice and of the liver in mice. No coherent evidence that styrene exposure increases risk from cancers of the lymphatic and hematopoietic tissue, pancreas, or lung was found [8]. About 90% of inhaled styrene is absorbed by the lung and undergoes biotransformation to styrene-7,8-oxide via cytochrome P-450s, which is further metabolized to mandelic acid (MA) and phenylglyoxylic acid (PGA). Being metabolized by the liver, styrene-induced toxicity may result in hepatic injury. It was reported that styrene caused an increase in serum level of direct bilirubin and direct/total bilirubin ratio, indicating diminished hepatic clearance of conjugated bilirubin
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