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

Environmental Carcinogenesis Unit, British Columbia Cancer Research Centre, and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1W5 Canada

Ferritin from horse spleen was found to cause severe chromosome aberrations in cultured Chinese hamster ovary cells. Ferritin at 15 to 170 µg/ml was 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 aberrations. Catalase and superoxide dismutase showed no inhibitory activity. The mechanism of DNA damage may involve reduction of Fe(III) in the ferritin core to Fe(II), followed by reoxidation of Fe(II) with possible formation of free radicals.

¹ This work was supported by the National Cancer Institute of Canada and the Natural Sciences and Engineering Research Council of Canada.

² Present address: Canadian Center for Occupational Health and Safety, Health Sciences Center, 3N25, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5.

³ To whom requests for reprints should be addressed.

Received 11/ 7/80. Accepted 1/22/81.

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