David Williams, Ph.D.
Oregon State University
NIEHS Grant P42ES016465
An NIEHS grantee and colleagues have developed a faster, more accurate method to assess cancer risk from exposure to polycyclic aromatic hydrocarbons (PAHs). People are primarily exposed to PAHs in the form of mixtures, and this proof-of-concept study demonstrates a first step towards moving away from risk assessments based on individual components of PAH mixtures to using methods that examine the whole mixture.
To determine the carcinogenic risk of PAH mixtures, the researchers measured the chemical bioactivity profile from skin cells of mice just after short-term PAH exposure. The bioactivity profile provides a unique fingerprint of genes and pathways activated by chemicals and mixtures after exposure and can be used for predicting long-term consequences such as cancer. They tested PAH mixtures found in coal tar, diesel exhaust, and cigarette smoke. After only 12 hours, the researchers could predict the ability of certain PAH mixtures to cause cancer, while other methods require waiting months for tumors to develop.
Although the method needs further testing, the findings demonstrate that long-term cancer outcome for PAH mixtures can be predicted by evaluating bioactivity after short-term exposure. Since the bioactivity profile provides gene signatures that are tied to chemical mechanism of action, this information could also provide insight into alternate mechanisms of PAH carcinogenesis and related mechanisms for complex mixtures.
Citation: Tilton SC, Siddens LK, Krueger SK, Larkin AJ, Löhr CV, Williams DE, Baird WM, Waters KM. 2015. Mechanism-based classification of PAH mixtures to predict carcinogenic potential. Toxicol Sci; doi:10.1093/toxsci/kfv080 [Online 22 April 2015].