Chromosome-damaging Activity of Ferritin and Its Relation to Chelation and Reduction of Iron1

Ferritin from horse spleen was found to cause severe chro mosome aberrations in cultured Chinese hamster ovary cells. Ferritin at 15 to 170 ji¿g/mlwas clastogenic and at higher doses was cytotoxic. At comparable concentrations of protein or iron, neither apoferritin nor complexed iron was clastogenic. Sulfhydryl compounds glutathione and cysteine reduced the cytotoxic and clastogenic activities of ferritin. Physiological concentrations of glutathione may normally be sufficient to protect cells from damage. The reducing agent ascorbate had little protective effect. Chelating agents varied in their inhibitory activity: ethylenediaminetetraacetic acid (hexadentate) > nitrilotriacetic acid (tetradentate) > salicylate (bidentate). 2,2'-Bipyridyl enhanced the chromosome-damaging action of ferritin while histidine did not markedly alter the frequencies of aber rations. Catalase and Superoxide dismutase showed no inhibi tory activity. The mechanism of DNA damage may involve reduction of Fe(lll) in the ferritin core to Fe(ll), followed by reoxidation of Fe(ll) with possible formation of free radicals.