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Suppression of chromosome aberrations in chromosome aberration syndromes by microcell mediated chromosome transfer

通过微细胞介导的染色体转移抑制染色体畸变综合征中的染色体畸变

基本信息

批准号：
61480437
负责人：
YOSHIDA Michihiro C.
金额：
$ 4.16万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

(1) Effect of the introduction of microcells into BS and FA cells: Microcells contained several numbers of chromosomes prepared from normal human diploid fibroblasts were fused to fibroblasts derived from Bloom syndrome (BS) or Faconi anemia (FA). Such fusions showed a dramatic reduction of each frequency of sister chromatid exchanges (SCEs) in BS-heterokaryons and of mitomcyin C (MMC)-induced chromosome aberrations (CAs) in FA-heterokaryons in comparison to that of parental BS of FA cells. The low levels of SCEs or MMC-induced CAs appeared in 2-day cultures after fusion and lasted fro several days, although a bimodal(high and low)level of SCEs in BS and MMC-induced CAs in FA heterokaryons was observed. The low level of SCEs or CAs in heterokaryons could be ascirbed to minicells that contained chromosomes reponsible for correction or suppression of BS- or FA-specific chromosome aberrations, while the transfer of minicells contained other chromosomes had no effect on suppression of the high levels of BS-specific SCEs or FA-specific CAs. Although it was not easy to identify chromosomes contributed to the normalization because of high frequency of pulverization of the transferred chromosomes, nos. 21 and 22 and sex chromosomes did not carry information of the normalization of BS-SCEs or FA-CAs. We are now trying to transfer minicells containing a single human chromosome prepared from man-mouse hybrid cells, in which human chromosomes had neo-marker.(2) Superoxide dismutase (SOD) activity in BS and FA cells: To elucidate the genotoxic action of active oxygen species (superoxide radicals, O^-_), activity of SOD was measured in BS and FA cells. An abnormally elevated SOD activity was found in bothe BS and FA cells, suggesting that an excess of O^-_ due to perturbation of oxygen metabolism in those cells may lead to the elevation of SOD activity, albeit insufficient to eliminate the high O^-_ levels, which results in enhanced chromosome damage.

(1)微细胞导入BS和FA细胞的效果：从正常人二倍体成纤维细胞制备的含有数条染色体的微细胞与源自Bloom综合征（BS）或Faconi贫血（FA）的成纤维细胞融合。这种融合表明，与FA细胞的亲本BS相比，BS-异核体中姐妹染色单体交换（sce）的频率和FA-异核体中丝裂细胞素C （MMC）诱导的染色体畸变（CAs）的频率显著降低。在融合后2天的培养中出现低水平的SCEs或mmc诱导的CAs，并持续数天，尽管在BS和mmc诱导的FA异核体中观察到双峰（高和低）水平的SCEs。异核体中低水平的SCEs或CAs可能归因于含有纠正或抑制BS或fa特异性染色体畸变的染色体的小细胞，而含有其他染色体的小细胞的转移对抑制高水平的BS特异性SCEs或fa特异性CAs没有影响。虽然由于转移染色体粉碎化频率高，不易鉴定为归一化的染色体，但21号、22号和性染色体不携带BS-SCEs或FA-CAs归一化的信息。我们现在正试图转移从人鼠杂交细胞中制备的含有单个人类染色体的微型细胞，其中人类染色体具有新标记。(2) BS和FA细胞超氧化物歧化酶（SOD）活性：为了阐明活性氧（超氧自由基，O^-_）的遗传毒性作用，我们测定了BS和FA细胞中SOD的活性。在BS和FA细胞中均发现异常升高的SOD活性，提示由于氧代谢紊乱导致的过量的O^-_可能导致SOD活性升高，但不足以消除高水平的O^-_，从而导致染色体损伤加剧。