Induction and repair inhibition of oxidative DNA damage by nickel(II) and cadmium(II) in mammalian cells

Carcinogenesis
H Dally, A Hartwig

Abstract

Compounds of nickel(II) and cadmium(II) are carcinogenic to humans and to experimental animals. One frequently discussed mechanism involved in tumor formation is an increase in reactive oxygen species by both metals with the subsequent generation of oxidative DNA damage. In the present study we used human HeLa cells to investigate the potential of nickel(II) and cadmium(II) to induce DNA lesions typical for oxygen free radicals in intact cells and the effect on their repair. As indicators of oxidative DNA damage, we determined the frequencies of DNA strand breaks and of lesions recognized by the bacterial formamidopyrimidine-DNA glycosylase (Fpg protein), including 7,8-dihydro-8-oxoguanine (8-hydroxyguanine), a pre-mutagenic DNA base modification. Nickel(II) caused a slight increase in DNA strand breaks at 250 microM and higher, while the frequency of Fpg-sensitive sites was enhanced only at the cytotoxic concentration of 750 microM. The repair of oxidative DNA lesions induced by visible light was reduced at 50 microM and at 100 microM nickel(II) for Fpg-sensitive sites and DNA strand breaks, respectively; the removal of both types of lesions was blocked nearly completely at 250 microM nickel(II). In the case of cadmium(II), DN...Continue Reading

Citations

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