Biomarkers of asphalt fume exposure.
Keshava-C; Keshava-N; Law-B; Lewis-D; Weston-A
Toxicologist 2004 Mar; 78(S-1):410
It has been estimated that at least 24,000 occupationally related cancers are diagnosed in the US each year. The introduction of occupational cancer biomarkers in cross-sectional epidemiologic research may be a useful approach in the development of strategies for intervention. Here we have used "gene chip" technology (high density DNA-oligonucleotide arrays) to identify potential biomarkers of asphalt fume condensate (AFC) exposure. A rat lung epithelial cell line (RLE-6TN) was exposed to AFC (270 ug/ml) in vitro for 12h and 24h. At the end of the treatment period, RNA was extracted from the cells, subjected to reverse transcription, in vitro transcription, fluorescence labeling and hybridization to Affymetrix rat genome microarrays (U34A). Transcription of 348 genes on the array was observed to be altered by a factor of at least 2 fold. A battery of genes induced (p<0.01) by this exposure included Phase I and II metabolism genes (CYP1A1, CYP1B1, GST-A1 and NQO1), oxidative stress and inflammatory genes (ALDH, CAT and COX-2), DNA damage response genes (GADD45, GADD153), and transcription factors and oncogenes (EIF-2 and FRA-1). These genes were selected for further investigation by reverse transcription and polymerase chain reaction (RT-PCR). The RT-PCR confirmed the induction of this battery of genes and RT-PCR was reasonably well correlated with the oligonucleotide array data (r 2 = 0.6, t = 3.3, p<0.01, df = 20). Genes that are turned-on in response to such exposures are potential candidate bio-markers that should be investigated further. This study identified several candidate biomarkers of asphalt fume exposure. Future studies will investigate the effects of chemopreventive agents on these candidate biomarkers and associated end-points like DNA damage in human epithelial cells.
Biomarkers; Asphalt-fumes; Exposure-levels; Occupational-diseases; Cancer; Epidemiology; Laboratory-animals; Animals; Animal-studies; In-vitro-studies; Genes; Lung-disorders; Pulmonary-system-disorders; Respiratory-system-disorders
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland