Wang Jin, Tian Xin, Zhang Jie, Tan Lirong, Ouyang Nan, Jia Beibei, Chen Chunying, Ge Cuicui, Li Jianxiang
Department of Toxicology, School of Public Health, Medicine College, Soochow University, Suzhou 215123, China.
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
ACS Nano. 2021 Apr 27;15(4):7094-7104. doi: 10.1021/acsnano.1c00239. Epub 2021 Mar 24.
As environmental pollutants and possible carcinogens, carbon nanotubes (CNTs) have recently been found to induce carcinogenesis and tumor metastasis after long-term pulmonary exposure. However, whether CNT-induced carcinogenesis can be inherited and last for generations remains unclear. Herein, postchronic single-walled carbon nanotubes (SWCNTs) exposed human lung cell model (BEAS-2B cells) are established to investigate SWCNT-induced carcinogenesis. At a tolerated sublethal dose level, postchronic SWCNT exposure significantly increases the migration and invasion abilities of BEAS-2B cells, leading to malignant cell transformation. Notably, the malignant transformation of BEAS-2B cells is irreversible within a 60 day recovery period after SWCNT exposure, and the malignant transformation activities of cells gradually increase during the recovery period. Moreover, these transformed cells promote carcinogenesis , accompanied by a raised level of biomarkers of lung adenocarcinoma. Further mechanism analyses reveal that postchronic exposure to SWCNTs causes substantial DNA methylation and transcriptome dysregulation of BEAS-2B cells. Subsequent enrichment and clinical database analyses reveal that differentially expressed/methylated genes of BEAS-2B cells are enriched in cancer-related biological pathways. These results not only demonstrate that postchronic SWCNT-exposure-induced carcinogenesis is heritable but also uncover a mechanism from the perspective of DNA methylation.
作为环境污染物和潜在致癌物，碳纳米管（CNTs）最近被发现长期肺部暴露后会诱发癌症和肿瘤转移。然而，碳纳米管诱发的癌症是否会遗传并延续几代人仍不清楚。在此，建立了慢性单壁碳纳米管（SWCNTs）暴露后人肺细胞模型（BEAS-2B细胞）来研究SWCNT诱发的致癌作用。在可耐受的亚致死剂量水平下，慢性SWCNT暴露显著提高了BEAS-2B细胞的迁移和侵袭能力，导致恶性细胞转化。值得注意的是，SWCNT暴露后60天恢复期内BEAS-2B细胞的恶性转化是不可逆的，且细胞的恶性转化活性在恢复期逐渐增加。此外，这些转化细胞促进癌症发生，同时伴有肺腺癌生物标志物水平升高。进一步的机制分析表明，慢性暴露于SWCNTs会导致BEAS-2B细胞大量DNA甲基化和转录组失调。随后的富集和临床数据库分析表明，BEAS-2B细胞差异表达/甲基化的基因富集于癌症相关生物途径。这些结果不仅证明了慢性SWCNT暴露诱发的致癌作用是可遗传的，还从DNA甲基化角度揭示了一种机制。
