| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Double minutes (DMs) harboring the amplified oncogenes are found in a broad spectrum of human tumour cells. We previously found that the elimination of DMs led to the reversion of tumour cell phenotypes and the cellular differentiation. The previous studies suggested the selective incorporation of DMs into micronuclei mediates the elimination of DMs. However it remains to be uncovered how the content of micronuclei was eliminated. This study revealed that the micronuclei were extruded to the extracellular fluids, and just the mechanism explained the elimination of DMs quantitatively. The extracellular micronuclei were enriched with DMs, had apparently normal cytoplasmic membrane and nuclear membrane, and had undegraded DNA.Furthermore, we developed a quite physiological method for the purification of extracellular micronuclei. Based on these nature of the extracellular micronuclei, it seemed conceivable that the DMs might be transferred intercellularly through the medium of extracellul
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ar micronuclei. We examined this possibility thoroughly and carefully, however, by all means, we never succeeded the intercellular DM-transfer mediated by the extracellular micronuclei. On the other hand, it was also important to clarify the reason why the transfer was not possible. Therefore, we focused our attention to the intracellular motion that relates to the extracellular elimination of DMs, and obtained much achievement. Namely we uncovered the intranuclear unique motion of DMs which was coupled to the DNA replication. Acentric DMs are segregated to the daughter cells by the attachment to the mitotic chromosomes. We found that the detachment from the chromosome by the treatment of some drugs or the malfunctioning of p53 protein let DMs remain at the cytoplasm. In most cases, the cytoplasmic DMs attached to the nuclear membrane from the outside, were surrounded by the nuclear lamin proteins which the process led to the micronucleation at the S-phase. Consequently, the DMs in the micronuclei should be damaged which explained why the micronuclei-mediated DM-transfer was not successful. Less
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