Fe-rich chamosite in coal and lung cancer in Xuan Wei, China

Abstract

Xuan Wei, a county-level city from the southwestern Yunnan province, currently suffers the highest female lung cancer mortality rate in all of China. Male lung cancer mortality is also among the highest in China. Recent evidence indicates that indoor bituminous coal (smoky coal) burning shows a strong association with Xuan Wei lung cancer mortality. It is urgent to gain insight into the potential carcinogens and the underlying carcinogenesis mechanisms, in order to shed light on new targeted intervention approaches. The new carcinogen hypothesis of Fe-rich chamosite from Xuan Wei smoky coal combustion particles and the lung cancer epidemic in Xuan Wei were investigated in this thesis. It primarily addresses the three aims: 1) to prepare the Xuan Wei smoky coal combustion particles, and assess their characteristics; 2) to explore the newly suspected carcinogen (Fe-rich chamosite) and the underlying pathological mechanisms from Xuan Wei smoky coal, by inhalation toxicological models in vivo and in vitro; 3) to evaluate the intervention effects of the mitochondria-targeted iron chelation for Xuan Wei coal combustion particle exposure.

First, it is identified the Xuan Wei lung cancer mortality showed an increasing trend for the past five years, especially for females who were over 35 years old. The lung cancer began to spread from the highest-risk area in Xuan Wei geographically. Therefore, inhalation toxicological models and biomedical experiments are needed for further understanding of the carcinogenesis for Xuan Wei lung cancer. Then the Xuan Wei coal particles that could mimic the different-temperature combustion were prepared successfully through the epidemiological fieldwork. These samples were adopted to assess the carcinogenesis and inflammatory properties for the second research aim. Based on the findings, the bronchial epithelial cell lines malignant transformation was induced by the low-dose and long-term exposures to different thermal heating Xuan Wei coal particles. Moreover, significant up-regulations of Ferritin-L, Ferritin-H, Nrf2, and HO-1 protein and mRNA expressions in the antioxidant response element (ARE) pathway were induced by 250 ℃ and 550 ℃ PM sample exposure. The oxidative effects from Xuan Wei coal combustion particles exposure can be alleviated by deferiprone (DFP) gavage intervention significantly, which might provide us with a possible intervention strategy among the Xuan Wei residents.

In summary, by combinations of the multi-disciplinary research methods and particle inhalation models in vivo and in vitro from this thesis, Fe-rich chamosite from Xuan Wei smoky coal likely plays a significant role in the carcinogenesis pathway through activation of inflammatory reactions. The impacts could be intervened by intake of the mitochondria-targeted iron chelator (DFP) to some extent. Public concerns regarding the indoor air pollution induced by the coal combustion particles exposure should be prioritized for those at the high risk exposure. Appropriate actions may include encouraging the clean indoor solid fuel usage in Xuan Wei and other locations.