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.
Highlights
Nickel (Ni) is the 24 th most abundant element in Earth’s crust [1]
It has been suggested that synergistic DNA damage induced by simultaneous exposure of Ni compounds is possibly related to reactive oxygen species (ROS) [53,104,105]
In contrast to most studies, Kumar et al demonstrated that NiSO4 affected DNA replication and damaged DNA but did not induce any detectable ROS production in Escherichia coli, concluding that Ni-induced DNA damage is through an ROS-independent pathway [121]
Summary
Nickel (Ni) is the 24 th most abundant element in Earth’s crust [1]. On the one hand, at a low concentration, Ni is a nutritionally essential trace element for animals [2,3,4]. The International Agency for Research on Cancer (IARC) has classified Ni compounds such as nickel sulfate (NiSO4), nickel oxide (NiO), nickel hydroxides, and crystalline nickel as carcinogenic agents to humans (Group 1) [15]. It has been confirmed in many in vitro and vivo studies that Ni and Ni compounds have carcinogenicity [16,17,18,19,20,21,22].
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