Lehmann A R, Arlett C F, Broughton B C, Harcourt S A, Steingrimsdottir H, Stefanini M, Malcolm A, Taylor R, Natarajan A T, Green S
MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, United Kingdom.
Cancer Res. 1988 Nov 1;48(21):6090-6.
Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and physical retardation. Some patients are photosensitive. A previous study by Stefanini et al. (Hum. Genet., 74: 107-112, 1986) showed that cells from four photosensitive patients with TTD had a molecular defect in DNA repair, which was not complemented by cells from xeroderma pigmentosum, complementation group D. In a detailed molecular and cellular study of the effects of UV light on cells cultured from three further TTD patients who did not exhibit photosensitivity we have found an array of different responses. In cells from the first patient, survival, excision repair, and DNA and RNA synthesis following UV irradiation were all normal, whereas in cells from the second patient all these responses were similar to those of excision-defective xeroderma pigmentosum (group D) cells. With the third patient, cell survival measured by colony-forming ability was normal following UV irradiation, even though repair synthesis was only 50% of normal and RNA synthesis was severely reduced. The excision-repair defect in these cells was not complemented by other TTD cell strains. These cellular characteristics of patient 3 have not been described previously for any other cell line. The normal survival may be attributed to the finding that the deficiency in excision-repair is confined to early times after irradiation. Our results pose a number of questions about the relationship between the molecular defect in DNA repair and the clinical symptoms of xeroderma pigmentosum and TTD.
毛发硫营养不良症（TTD）是一种常染色体隐性疾病，其特征为毛发脆弱且含硫量降低、鱼鳞病、面容奇特以及智力和身体发育迟缓。部分患者对光敏感。斯特凡尼尼等人先前的一项研究（《人类遗传学》，74: 107 - 112，1986年）表明，4名患有TTD的光敏患者的细胞在DNA修复方面存在分子缺陷，而着色性干皮病D互补组患者的细胞无法对其进行互补。在对另外3名未表现出光敏性的TTD患者所培养细胞进行的紫外线光效应详细分子和细胞研究中，我们发现了一系列不同的反应。在第一名患者的细胞中，紫外线照射后的存活、切除修复以及DNA和RNA合成均正常，而在第二名患者的细胞中，所有这些反应都与切除缺陷型着色性干皮病（D组）细胞的反应相似。对于第三名患者，尽管修复合成仅为正常水平的50%且RNA合成严重减少，但通过集落形成能力测定的细胞存活在紫外线照射后是正常的。这些细胞中的切除修复缺陷无法被其他TTD细胞株互补。第三名患者的这些细胞特征此前在任何其他细胞系中均未被描述过。正常存活可能归因于切除修复缺陷仅限于照射后的早期这一发现。我们的结果引发了一些关于DNA修复分子缺陷与着色性干皮病和TTD临床症状之间关系的问题。
