HYPERSENSITIVITY TO MITOMYCIN-C CELL-KILLING IN ROBERTS SYNDROME FIBROBLASTS WITH, BUT NOT WITHOUT, THE HETEROCHROMATIN ABNORMALITY
HYPERSENSITIVITY TO MITOMYCIN-C CELL-KILLING IN ROBERTS SYNDROME FIBROBLASTS WITH, BUT NOT WITHOUT, THE HETEROCHROMATIN ABNORMALITY
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DOI：
10.1016/0165-1161(89)90049-6
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发表时间：
1989-10-01
期刊：
影响因子：
--
通讯作者：
TOMKINS, DJ
中科院分区：
文献类型：
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作者：
BURNS, MA;TOMKINS, DJ
罗伯茨综合征（RS）是一种罕见的遗传性疾病，其临床特征是严重的产前和产后发育迟缓和对称性肢体缩短畸形。某些RS患者具有独特的组成性异染色质异常（RS效应），其被描述为染色体的近着丝粒和核仁组织区与Y染色体长臂的远端部分过早分离（German，1979）。这些患者[表示为RS（+）]在临床上与缺乏Roberts综合征细胞遗传学标记的RS（-）患者难以区分。最近，已经描述了果蝇中的突变体，其具有异染色质欠缩合和对诱变剂处理的超敏性（Gatti等人，1983年）。作者认为，未凝聚的异染色质可能更容易受到诱变剂的损伤。因此，本研究调查了Roberts综合征的诱变剂敏感性，以确定异染色质结构异常与诱变剂敏感性之间是否存在类似的关系。用RS（+）成纤维细胞、RS（-）成纤维细胞、RS杂合成纤维细胞和大量适当对照细胞进行平板接种效率实验。异染色质异常的RS成纤维细胞对丝裂霉素C处理的敏感性（基于D10值）始终高于任何其他检测的细胞株，包括RS（-）细胞。这些结果支持Roberts综合征中丝裂霉素C敏感性和异染色质结构异常相关的假设。
Roberts syndrome (RS) is a rare genetic disorder, characterized clinically by severe pre- and post-natal growth retardation and symmetric limb reduction deformities. Some patients with RS have a distinctive abnormality of the constitutive heterochromatin (the RS effect) which has been described as a premature separation of the paracentromeric and nucleolar organizing regions of the chromosomes and the distal portion of the long arm of the Y chromosome (German, 1979). These patients [denoted RS(+)] are clinically indistinguishable from the RS(-) patients who lack the cytogenetic marker for Roberts syndrome. Recently, mutant in Drosophila has been described which has both heterochromatin undercondensation and hypersensitivity to mutagen treatment (Gatti et al., 1983). The authors suggested that the uncondensed heterochromatin may be more accessible to damage by mutagens. Thus, the present study was an investigation of the mutagen sensitivity in Roberts syndrome, to determine whether there is a similar relationship between abnormal heterochromatin structure and mutagen sensitivity. Plating efficiency experiments were performed with RS(+) fibroblasts, RS(-) fibroblasts, RS heterozygous fibroblasts and a large assortment of appropriate control cells. The RS fibroblasts with the heterochromatin abnormality were consistently more sensitive (based on D10 values) to mitomycin C treatment than were any of the other cell strains tested, including RS(-) cells. These results support the hypothesis that mitomycin C sensitivity and abnormal heterochromatin structure in Roberts syndrome are related.