Oxidative and nitrative DNA damage induced by industrial chemicals in relation to carcinogenesis. in Journal of occupational health / J Occup Health. 2025 Jan 24:uiaf003. doi: 10.1093/joccuh/uiaf003.

2025

Tipo pubblicazione

Journal Article;

Autori/Collaboratori (1)

Hiraku Y
Department of Environmental Health, University of Fukui School of Medical Science, Eiheiji, Fukui, Japan.

Abstract

OBJECTIVES: Many chemicals have been used for industrial purposes, and some of them are carcinogenic to humans. However, their molecular mechanisms have not been well understood. Reactive oxygen species are generated from industrial chemicals and contribute to carcinogenesis. Particles and fibers are accumulated in respiratory systems by inhalation exposure and cause chronic inflammation. Under inflammatory conditions, reactive nitrogen species are generated from inflammatory and epithelial cells. These species cause oxidative and nitrative DNA damage, leading to carcinogenesis. We carried out experiments on DNA damage induced by various industrial chemicals and investigated their molecular mechanisms. METHODS: We examined oxidative DNA damage induced by industrial chemicals using DNA fragments derived from human cancer-relevant genes by polyacrylamide gel electrophoresis. We also examined the formation of 8-nitroguanine (8-nitroG), a DNA lesion formed under inflammatory conditions, in lung tissues and cultured cells exposed to industrial chemicals by immunohistochemistry and immunocytochemistry. RESULTS: Benzene and o-toluidine metabolites caused oxidative damage to DNA fragments in the presence of Cu(II). H2O2 and Cu(I) were generated during oxidation of these chemicals and involved in DNA damage. 8-NitroG formation was observed in lung tissues of asbestos-exposed mice and humans. Carbon nanomaterials and indium compounds induced 8-nitroG formation in human lung epithelial cells via the release of damage-associated molecular patterns from exposed cells. CONCLUSIONS: Various industrial chemicals are considered to induce carcinogenesis by causing oxidative and nitrative DNA damage. These findings would provide an insight into risk assessment of industrial chemicals and prevention of carcinogenesis that occurs in workplaces.

PMID : 39853239

DOI : 10.1093/joccuh/uiaf003