Williams G M, Klaiber M, Parker S E, Farber E
J Natl Cancer Inst. 1976 Jul;57(1):157-65. doi: 10.1093/jnci/57.1.157.
A technique for induction of iron accumulation in hepatocytes of rats was used to identify early carcinogen-induced lesions by their histochemical absence of iron. Foci of iron-free altered hepatocytes produced by the feeding of N-2-fluorenylacetamide (FAA) for 3 weeks were composed of cells that were replicating when surrounding iron-containing hepatocytes were not, and that responded to a mitotic stimulus when surrounding hepatocytes were inhibited or showed a delayed response. Thus these lesions represented focal hyperplastic overgrowths. The iron-free hyperplastic foci developed into hyperplastic areas that progressed with longer feeding of FAA to form hyperplastic nodules. The lack of iron was a sensitive and reliable marker for hyperplastic lesions, which also permitted their identification in the fresh state. Both early hyperplastic lesions and nodules were often resistant to the necrogenic effects of dimethylnitrosamine, as well as to the antireplicative effect of FAA. The selection of such cells resistant to the toxic effects of carcinogens may be important in the pathogenesis of liver neoplasia.
一种诱导大鼠肝细胞铁蓄积的技术被用于通过组织化学方法鉴定早期致癌物诱导的病变，这些病变缺乏铁。通过喂食N-2-芴基乙酰胺（FAA）3周产生的无铁改变肝细胞灶由这样的细胞组成：当周围含铁肝细胞不复制时它们在复制，并且当周围肝细胞受到抑制或显示延迟反应时它们对有丝分裂刺激有反应。因此，这些病变代表局灶性增生性过度生长。无铁增生灶发展为增生区域，随着FAA喂食时间延长，这些增生区域进一步发展形成增生结节。铁的缺乏是增生性病变的一个敏感且可靠的标志物，这也使得它们能够在新鲜状态下被识别。早期增生性病变和结节通常对二甲基亚硝胺的致坏死作用以及FAA的抗复制作用具有抗性。选择这种对致癌物毒性作用具有抗性的细胞可能在肝脏肿瘤发生机制中具有重要意义。
