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

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(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.