Carcinogenic Risk Assessment of Polycyclic Aromatic Hydrocarbons in the Ambient Air Using In Vivo Mutagenicity Data
摘要
Polycyclic aromatic hydrocarbons (PAHs) and their related compounds absorbed on airborne particles are suspected of causing lung cancer, and it is necessary to develop the approaches for assessing the carcinogenic risk of PAHs. In the 1990s, we observed that the level of DNA adducts was dramatically increased in the lungs of rats after 4-week inhalation of ambient air from the Tokyo metropolitan area. This observation led us to evaluate the in vivo mutagenicity of airborne particles and their components by means of transgenic mouse gene mutation assay (gpt delta mouse), and we found elevated mutation frequency in the lungs of mice exposed to diesel exhaust or diesel exhaust particles. We then conducted a real-world study to evaluate the in vivo mutagenicity of airborne particles containing a mixture of PAHs. Extracts from airborne particles collected in 1980, 1990, and 2010 from the Tokyo metropolitan area were instilled to gpt delta mouse lungs, and the 1990 extract showed the most potent in vivo mutagenicity. In addition, G-to-T transversion, a landmark mutation of oxidative stress, was markedly induced in the extract-instilled lungs. Our findings indicate that the carcinogenic risk of PAHs absorbed on airborne particles can be quantitatively assessed from in vivo mutagenicity.