Whiting R F, Wei L, Stich H F
Cancer Res. 1981 May;41(5):1628-36.
Ferritin from horse spleen was found to cause severe chromosome aberrations in cultured Chinese hamster ovary cells. Ferritin at 15 to 170 microgram/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) greater than nitrilotriacetic acid (tetradentate) greater than salicylate (bidentate). 2,2'-Bipyridyl enhance 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.
研究发现，来自马脾的铁蛋白可在培养的中国仓鼠卵巢细胞中引起严重的染色体畸变。浓度为15至170微克/毫升的铁蛋白具有致断裂作用，而在更高剂量时具有细胞毒性。在蛋白质或铁浓度相当的情况下，脱铁铁蛋白和络合铁均无致断裂作用。巯基化合物谷胱甘肽和半胱氨酸可降低铁蛋白的细胞毒性和致断裂活性。生理浓度的谷胱甘肽通常可能足以保护细胞免受损伤。还原剂抗坏血酸几乎没有保护作用。螯合剂的抑制活性各不相同：乙二胺四乙酸（六齿）大于次氮基三乙酸（四齿）大于水杨酸盐（双齿）。2,2'-联吡啶增强了铁蛋白的染色体损伤作用，而组氨酸并未显著改变畸变频率。过氧化氢酶和超氧化物歧化酶无抑制活性。DNA损伤的机制可能涉及铁蛋白核心中的Fe(III)还原为Fe(II)，随后Fe(II)再氧化，可能形成自由基。
