Abstract：
Cytogenetic studies have shown that human chromosomes 1, 9, and 16, with a large heterochromatic region of highly methylated classical satellite DNA, are prone to induction of chromatid breaks and interchanges by mitomycin C (MMC). A couple of studies have indicated that material from chromosome 9, and possibly also from chromosomes 1 and 16, are preferentially micronucleated by MMC. Here, we further examined the chromosome-specific induction of micronuclei (MN; with and without cytochalasin B) and chromosomal aberrations (CAs) by MMC. Cultures of isolated human lymphocytes from two male donors were treated (at 48 h of culture, for 24 h) with MMC (500 ng/ml), and the induced MN were examined by a pancentromeric DNA probe and paint probe for chromosome 9, and by paint probes for chromosomes 1 and 16. MMC increased the total frequency of MN by 6-8-fold but the frequency of chromosome 9 -positive (9+) MN by 29-30-fold and the frequency of chromosome 1 -positive (1+) MN and chromosome 16 -positive (16+) MN by 12-16-fold and 10-17-fold, respectively. After treatment with MMC, 34-47 % of all MN were 9+, 17-20 % 1+, and 3-4 % 16+. The majority (94-96 %) of the 9+ MN contained no centromere and thus harboured acentric fragments. When MMC-induced CAs aberrations were characterized by using the pancentromeric DNA probe and probes for the classical satellite region and long- and short- arm telomeres of chromosome 9, a high proportion of chromosomal breaks (31 %) and interchanges (41 %) concerned chromosome 9. In 83 % of cases, the breakpoint in chromosome 9 was just below the region (9cen-q12) labelled by the classical satellite probe. Our results indicate that MMC specifically induces MN harbouring fragments of chromosome 9, 1, and 16. CAs of chromosome 9 are highly overrepresented in metaphases of MMC-treated lymphocytes. The preferential breakpoint is below the region 9q12.
摘要：
细胞遗传学研究表明，人类染色体1，9和16，具有高度甲基化的经典卫星DNA的大异色区域，丝裂霉素C（MMC）容易诱导染色单体断裂和互换。几项研究表明，来自9号染色体以及可能来自1号和16号染色体的物质优先被MMC微核化。这里,我们进一步检查了MMC对微核（MN；有或没有细胞松弛素B）和染色体畸变（CA）的染色体特异性诱导。处理来自两名男性供体的分离的人淋巴细胞的培养物（在培养48小时时，24小时）与MMC（500ng/ml），并通过9号染色体的pancentromericDNA探针和油漆探针以及1号和16号染色体的油漆探针检查诱导的MN。MMC使MN的总频率增加了6-8倍，但9号染色体阳性（9）MN的频率增加了29-30倍，1号染色体阳性（1）MN和16号染色体阳性（16）MN的频率增加了12-16倍和10-17倍，分别。用MMC治疗后，所有MN的34-47%为9+，17-20%1+，和3-4%16+。9MN中的大多数（94-96％）不含着丝粒，因此带有无心片段。当MMC诱导的CAs畸变通过使用9号染色体的经典卫星区域和长臂和短臂端粒的探针和探针来表征时，染色体断裂的比例很高（31％）和互换（41％）涉及9号染色体。在83%的案例中，9号染色体上的断点正好在经典卫星探针标记的区域（9cen-q12）下方。我们的结果表明，MMC特异性诱导携带9号、1号和16号染色体片段的MN。9号染色体的CA在MMC处理的淋巴细胞的中期中高度过量。优先断点低于9q12区域。
