Emerit I, Levy A, Pagano G, Pinto L, Calzone R, Zatterale A
Centre de Recherches Biomédicales des Cordeliers, CNRS, Paris, France.
Hum Genet. 1995 Jul;96(1):14-20. doi: 10.1007/BF00214180.
The present study was conducted on 13 patients with Fanconi anemia. 25 parents and 12 siblings. The chromosomal instability characteristic of this congenital breakage syndrome was associated with the presence of transferable clastogenic material in the plasma, as also reported previously for ataxia telangiectasia and Bloom's syndrome. While all plasma ultrafiltrates from homozygotes had chromosome damaging properties, the clastogenic material had to be concentrated in most heterozygotes to reach detectable levels. The clastogenic effect was exerted via the intermediacy of superoxide radicals, since it was regularly inhibited by superoxide dismutase (SOD). This adds further evidence for a prooxidant state in this hereditary disease. The autosustained clastogenic activity possibly plays a role in the progressive impairment of blood cell-producing bone marrow and may predispose patients to develop cancer and leukemia. Prophylactic use of antioxidants may be recommended, using clastogenic plasma activity as a guide.
本研究对13例范可尼贫血患者、25名父母及12名兄弟姐妹进行了研究。这种先天性断裂综合征的染色体不稳定特征与血浆中可转移的致染色体断裂物质的存在有关，这与先前报道的共济失调毛细血管扩张症和布卢姆综合征情况相同。虽然纯合子的所有血浆超滤物都具有染色体损伤特性，但在大多数杂合子中，致染色体断裂物质必须浓缩才能达到可检测水平。致染色体断裂作用是通过超氧自由基介导的，因为它经常被超氧化物歧化酶（SOD）抑制。这为这种遗传性疾病中的促氧化状态提供了进一步的证据。这种自身维持的致染色体断裂活性可能在产生血细胞的骨髓进行性损伤中起作用，并可能使患者易患癌症和白血病。可建议预防性使用抗氧化剂，以血浆致染色体断裂活性为指导。
