In vitro genotoxicity of asbestos substitutes induced by coupled stimulation of dissolved high-valence ions and oxide radicals
The wide use of asbestos and its substitutes has given rise to studies on their possible harmful effects on human health and environment. However, their toxic effects remain unclear. The present study was aimed to disclose the coupled effects of dissolved high-valence ions and oxide radicals using the in vitro cytotoxicity and genotoxicity of chrysotile (CA), nano-SiO2 (NS), ceramic fiber (CF), glass fiber (GF), and rock wool (RW) on Chinese hamster lung cells V79. All samples induced cell mortality correlated well with the chemical SiO2 content of asbestos substitutes and the amount of dissolved Si. Alkali or alkaline earth metal elements relieved mortality of V79 cells; Al2O3 reinforced toxicity of materials. Asbestos substitutes generated lasting, increasing amount of acellular ·OH which formed at the fiber surface at sites with loose/unsaturated bonds, as well as by catalytic reaction through dissolved iron. Accumulated mechanical and radical stimulation induced the intracellular reactive oxygen species (ROS) elevation, morphology change, and deviating trans-membrane ion flux. The cellular ROS appeared as NS > GF > CF ≈ CA > RW, consistent with cell mortality rather than with acellular ·OH generation. Chromosomal and DNA lesions in V79 cells were not directly associated with the cellular ROS, while influenced by dissolved high-valence irons in the co-culture medium. In conclusion, ions from short-time dissolution of dust samples and the generation of extracellular ·OH presented combined effects in the elevation of intracellular ROS, which further synergistically induced cytotoxicity and genotoxicity.
KeywordsChrysotile Asbestos substitutes Dissolved ions Hydroxyl radical Reactive oxygen species Cytotoxicity and genotoxicity
This study was founded by projects of the National Natural Science Foundation of China (41130746, 41602033 and 41472046). The authors would like to thank the preclinical medicine laboratory of Southwest Medical University for its support in the experiment. Specially, the authors would like to express heartfelt gratitude to Dr. Maarten A.T.M. Broekmans for his kind, patient, and valuable suggestions for this manuscript’s improvement.
All authors contributed to this manuscript. Faqin Dong and Jianjun Deng conceived and designed the study. Tingting Huo, Wei Ye, and Pingping Wang performed the experiments. Wei Zhang performed the data analysis. Tingting Huo wrote this manuscript. Faqin Dong, Qingbi Zhang, and Dongping Sun guided the structure and contents of the paper and improved earlier drafts.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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