Hye Lim KimYeo Jin KimNam Gook KeePreeyaporn KoedrithYoung Rok SeoNational Forensic Service, Republic of KoreaFaculty of Environment and Resource Studies, Mahidol UniversityDongguk University, Gyeongju2022-08-042022-08-042021-04-01Molecular and Cellular Toxicology. Vol.17, No.2 (2021), 169-177209284671738642X2-s2.0-85102527802https://repository.li.mahidol.ac.th/handle/20.500.14594/77054Backgrounds: Nickel is known as a carcinogen through the environmental and occupational exposures. One of carcinogenic mechanisms of nickel is an induction of oxidative stresses and inhibition of DNA repair. But the exact molecular mechanisms by which nickel induces carcinogenicity remains unclear. Objectives: We selected the sub-lethal dose of nickel in human cells using MTT assay and FACS analysis. To demonstrate the effect of nickel on transcriptional activity of p53, we conducted an electrophoretic mobility shift assay and streptavidin magnetic bead assay. Gadd45a–APE1 complex was confirmed by in situ proximity ligation assay. Results: We demonstrated that nickel can interfere with the physical interaction between Gadd45a and APE1, in vitro and in situ, as well as APE1 activity in vitro. Conclusion: Our study implies that the inhibition of p53-mediated APE1 activity in base excision repair might be suggested as one of the potential carcinogenic mechanisms in response to nickel even at a low dose.Mahidol UniversityEnvironmental ScienceMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1007/s13273-021-00122-z