Oxidative and nitrative DNA damage induced by industrial chemicals in relation to carcinogenesis.

OBJECTIVES

Many chemicals have been used for industrial purposes, and some of them are carcinogenic to humans. However, the molecular mechanisms of their carcinogenetic effects 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. Using immunohistochemistry and immunocytochemistry 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.

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 provide an insight into risk assessment of industrial chemicals and prevention of carcinogenesis in workplaces.