Bender M A, Viola M V, Fiore J, Thompson M H, Leonard R C
Medical Department, Brookhaven National Laboratory, Upton, New York 11973.
Cancer Res. 1988 May 1;48(9):2579-84.
Recent reports have suggested that elevated chromosomal aberration yields following X-irradiation of skin fibroblasts in the G2 phase of the cell cycle are characteristic of affected members of cancer-prone families. These studies propose that this phenomenon is a consequence of impaired DNA repair and might be a useful predictor of genetic susceptibility to cancer. We have tested G2 chromosomal X-ray sensitivity in skin fibroblasts and peripheral blood lymphocytes from members of a kindred with the cancer family syndrome, a disorder in which susceptibility to colon cancer and other epithelial cancers is inherited in an autosomal dominant pattern. Further, using a cell survival assay, we tested cancer family syndrome skin fibroblasts for sensitivity to four classes of mutagens, including X-rays. In the assays used, skin fibroblasts and lymphocytes from both affected and unaffected family members exhibited responses indistinguishable from normal controls. Karyotypic analysis of lymphocytes and fibroblasts revealed no consistent constitutional cytogenetic abnormality. Thus, affected patients with the cancer family syndrome do not have increased sensitivity to irradiation and chemical mutagens and lack a germ-line chromosomal defect.
最近的报告表明,处于细胞周期G2期的皮肤成纤维细胞经X射线照射后染色体畸变率升高是癌症高发家族中患病成员的特征。这些研究提出,这种现象是DNA修复受损的结果,可能是癌症遗传易感性的一个有用预测指标。我们检测了患有癌症家族综合征(一种结肠癌和其他上皮癌易感性以常染色体显性模式遗传的疾病)家族成员的皮肤成纤维细胞和外周血淋巴细胞对G2期染色体X射线的敏感性。此外,我们使用细胞存活试验,检测了癌症家族综合征皮肤成纤维细胞对包括X射线在内的四类诱变剂的敏感性。在所使用的检测中,患病和未患病家族成员的皮肤成纤维细胞和淋巴细胞表现出与正常对照无差异的反应。淋巴细胞和成纤维细胞的核型分析未发现一致的先天性细胞遗传学异常。因此,患有癌症家族综合征的患者对辐射和化学诱变剂没有增加的敏感性,也不存在种系染色体缺陷。