Susan Tilton, Ph.D.
Oregon State University
NIEHS-funded scientists have developed a method to better predict the cancer-causing potential of polycyclic aromatic hydrocarbons (PAHs), a class of more than 1,500 chemicals that result from combustion of organic matter and fossil fuels. PAH exposures occur as complex environmental mixtures, making it difficult to tease apart the cancer-causing potential of individual chemicals in the mixture.
The researchers exposed a 3D model of human lung tissue to individual PAHs and identified genes with altered expression following exposure. Using computational approaches, they grouped the genes into gene sets related to specific biological pathways. They then looked for gene sets that were consistent across PAH chemicals with similar cancer-causing potential.
More than 9,500 genes were differentially expressed in PAH-exposed tissue compared to controls. The researchers identified four genes sets that, when combined, best predicted PAH carcinogenicity. These gene sets were related to pathways involved in cell differentiation processes, blood vessel formation, cell cycle regulation, and aryl hydrocarbon receptor signaling, which is important in the body’s response to environmental pollutants. Notably, the gene sets that were most affected by exposure to the PAH chemical benzo[a]pyrene (BAP) did not overlap with the four gene sets that best classified PAH carcinogenicity. This result challenges current risk assessment methods, which assume the mechanisms by which BAP causes cancer are representative of other carcinogenic PAHs.
According to the authors, results support the use of pathway-based gene sets and 3D human tissue models to better predict the cancer-causing potential of PAHs.
Citation: Chang Y, Huynh CTT, Bastin KM, Rivera BN, Siddens LK, Tilton SC. 2020. Classifying polycyclic aromatic hydrocarbons by carcinogenic potency using in vitro biosignatures. Toxicol In Vitro 69:104991.