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 su bacute environmental concentrations in experimental animals. We invest igated the potential of cadmium(II) to induce oxidative DNA damage in brain cell cultures obtained from larvae of Pleurodeles waltl. As indi cators of DNA lesions typical of oxygen free radicals, we determined t he frequencies of DNA strand breaks and of DNA base modifications reco gnized by the bacterial formamidopyrimidine - DNA glycosylase (Fpg pro tein). DNA strand breaks were generated in a dose-dependent manner at concentrations of 1 mu M and greater. In contrast, no significant incr ease in Fpg-sensitive sites was observed under our experimental condit ions. However, the repair of Fpg-sensitive DNA lesions induced by visi ble light was slightly diminished at 1 mu M and inhibited completely a t 10 mu M of cadmium(II), while the closure of DNA strand breaks was n ot affected. Our results show that, although cadmium is not able to in duce 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 neu rotoxicity of this metal. (C) 1998 Elsevier Science Ireland Ltd. All r ights reserved.