Application of oligonucleotide microarray technology to toxic occupational exposures

Microarray technology has advanced toward analysis of toxic occupational exposures in biological systems. Microarray analysis is an ideal way to search for biomarkers of exposure, even if no specific gene or pathway has been identified. Analysis may now be performed on thousands of genes simultaneously, as opposed to small numbers of genes as in the past. This ability has been put to use to analyze gene expression profiles of a variety of occupational toxins in animal models to classify toxins into specific categories based on response. Analysis of normal human cell strains allows an extension of this analysis to investigate the role of interindividual variation in response to various toxins. This methodology was used to analyze four occupationally related toxins in our lab: oxythioquinox (OTQ), a quinoxaline pesticide; malathion, an organophosphate pesticide; di-n-butyl phthalate (DBP), a chemical commonly found in personal care and cosmetic items; and benzo[a]pyrene (BaP), an environmental and occupational carcinogen. The results for each exposure highlighted signaling pathways involved in response to these occupational exposures. Both pesticides showed increase in metabolic enzymes, while DBP showed alterations in genes related to fertility. BaP exposure showed alterations in two cytochrome P450s related to carcinogenicity. When used with occupational exposure information, these data may be used to augment risk assessment to make the workplace safer for a greater proportion of the workforce, including individuals susceptible to disease related to exposures.