Effect of cadmium(II) on the extent of oxidative DNA damage in primary brain cell cultures from Pleurodeles larvae.
Compounds of cadmium(II) are well-known human and animal carcinogens. Furthermore, they affect development. growth and brain functions at subacute environmental concentrations in experimental animals. We investigated the potential of cadmium(II) to induce oxidative DNA damage in brain cell cultures obtained from larvae of Pleurodeles waltl. As indicators of DNA lesions typical of oxygen free radicals, we determined the frequencies of DNA strand breaks and of DNA base modifications recognized by the bacterial formamidopyrimidine-DNA glycosylase (Fpg protein). DNA strand breaks were generated in a dose-dependent manner at concentrations of 1 microM and greater. In contrast, no significant increase in Fpg-sensitive sites was observed under our experimental conditions. However, the repair of Fpg-sensitive DNA lesions induced by visible light was slightly diminished at 1 microM and inhibited completely at 10 microM of cadmium(II), while the closure of DNA strand breaks was not affected. Our results show that, although cadmium is not able to induce oxidative DNA base modifications in larval brain cells directly, its capability to generate DNA strand breaks and to interfere with the repair of oxidative DNA damage could explain the early life stage neurotoxicity of this metal.
Calevro
F
F
Department of Biology and Chemistry, University of Bremen, Germany.
Beyersmann
D
D
Hartwig
A
A
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019256:Cadmium Chloride / Q000633:toxicity*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000187:drug effects*; D043382:DNA-Formamidopyrimidine Glycosylase; D007814:Larva; D008027:Light; D009153:Mutagens / Q000633:toxicity*; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D010999:Pleurodeles; D013481:Superoxides
D004277:DNA, Single-Stranded; D009153:Mutagens; D013481:Superoxides; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D019256:Cadmium Chloride