Effects of zinc on the binding of cadmium to DNA: Assessment with testicular interstitial cell and calf thymus DNAs.
To clarify the mechanism of the protective action of zinc against the tumorigenicity of cadmium in rat testes, the effect of in vivo zinc pretreatment (zinc acetate, 1.0 mmol/kg, sc, 24 hr before the examination) on in vitro binding of cadmium to rat testicular interstitial cell (IC) DNA was studied. The competition between zinc and cadmium for binding to purified calf thymus DNA, as assessed by acridine orange dye binding, was also examined. In vivo zinc pretreatment significantly elevated the level of zinc in DNA isolated from ICs and reduced binding of cadmium to DNA following in vitro exposure. Both zinc and cadmium individually inhibited the formation of the acridine orange dye and calf thymus DNA complex, although co-operative inhibition with co-exposure was not observed. It is known that zinc has a higher affinity for the phosphate groups of DNA than does cadmium, which favours base binding, and that interactions with the phosphate groups of DNA stabilize the macromolecule structure. The present data suggest that zinc may, in part, prevent tumorigenicity of cadmium in rat testes by reducing its binding to DNA through a structural stabilization as well as through direct competition for binding sites.
Koizumi
T
T
Faculty of Pharmaceutical Sciences, Chiba University, 1-33, Yayoi-cho, Chiba 260, Japan.
Waalkes
M P
MP