Nickel Carcinogenesis Mechanism: DNA Damage

Guo, Hongrui; Liu, Huan; Wu, Hongbin; Cui, Hengmin; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Li, Yinglun; Wang, Xun; Zhao, Ling

doi:10.3390/ijms20194690

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Nickel Carcinogenesis Mechanism: DNA Damage

by

Hongrui Guo

^1,2,†,

Huan Liu

^1,†,

Hongbin Wu

^1,†,

Hengmin Cui

^1,2,3,*

,

Jing Fang

^1,2,

Zhicai Zuo

^1,2,

Junliang Deng

^1,2,

Yinglun Li

^1,2,

Xun Wang

^1,2 and

Ling Zhao

^1,2

¹

College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China

²

Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu 611130, China

³

Key Laboratory of Agricultural information engineering of Sichuan Province, Sichuan Agriculture University, Yaan 625014, Sichuan, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2019, 20(19), 4690; https://doi.org/10.3390/ijms20194690

Submission received: 23 August 2019 / Revised: 15 September 2019 / Accepted: 20 September 2019 / Published: 21 September 2019

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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Abstract

Nickel (Ni) is known to be a major carcinogenic heavy metal. Occupational and environmental exposure to Ni has been implicated in human lung and nasal cancers. Currently, the molecular mechanisms of Ni carcinogenicity remain unclear, but studies have shown that Ni-caused DNA damage is an important carcinogenic mechanism. Therefore, we conducted a literature search of DNA damage associated with Ni exposure and summarized known Ni-caused DNA damage effects. In vitro and vivo studies demonstrated that Ni can induce DNA damage through direct DNA binding and reactive oxygen species (ROS) stimulation. Ni can also repress the DNA damage repair systems, including direct reversal, nucleotide repair (NER), base excision repair (BER), mismatch repair (MMR), homologous-recombination repair (HR), and nonhomologous end-joining (NHEJ) repair pathways. The repression of DNA repair is through direct enzyme inhibition and the downregulation of DNA repair molecule expression. Up to now, the exact mechanisms of DNA damage caused by Ni and Ni compounds remain unclear. Revealing the mechanisms of DNA damage from Ni exposure may contribute to the development of preventive strategies in Ni carcinogenicity.

Keywords: Ni; carcinogenicity; DNA damage; ROS; DNA damage repair

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MDPI and ACS Style

Guo, H.; Liu, H.; Wu, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Nickel Carcinogenesis Mechanism: DNA Damage. Int. J. Mol. Sci. 2019, 20, 4690. https://doi.org/10.3390/ijms20194690

AMA Style

Guo H, Liu H, Wu H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L. Nickel Carcinogenesis Mechanism: DNA Damage. International Journal of Molecular Sciences. 2019; 20(19):4690. https://doi.org/10.3390/ijms20194690

Chicago/Turabian Style

Guo, Hongrui, Huan Liu, Hongbin Wu, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, and Ling Zhao. 2019. "Nickel Carcinogenesis Mechanism: DNA Damage" International Journal of Molecular Sciences 20, no. 19: 4690. https://doi.org/10.3390/ijms20194690

APA Style

Guo, H., Liu, H., Wu, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2019). Nickel Carcinogenesis Mechanism: DNA Damage. International Journal of Molecular Sciences, 20(19), 4690. https://doi.org/10.3390/ijms20194690

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