Eul J, Gronemeyer H, Adolph S, Hameister H
Abteilung Klinische Genetik, Universität Ulm, Federal Republic of Germany.
Chromosoma. 1988;96(3):248-54. doi: 10.1007/BF00302364.
Intraspecific somatic cell hybrids between T-lymphoma cells and lymphocytes are highly tumorigenic whereas fusion of T-lymphoma cells with normal fibroblasts leads to reduced or even completely suppressed tumorigenicity of the hybrid cells. A particular cytogenetic phenomenon defines these two classes of hybrids. DNA replication analysis via bromodeoxyuridine pulse labelling reveals an aberrant banding pattern in the c-myc chromosomal domain in tumour cells and highly tumorigenic hybrids. In hybrids with suppressed tumorigenicity the tumor parent derived chromosomes have reverted to normal DNA replication banding. Aberrant DNA replication in tumour cells and highly tumorigenic hybrids coincides with enhanced c-myc expression. In hybrids with suppressed tumorigenicity and with normal DNA replication banding c-myc expression is also reduced. Thus, a correlation between aberrant DNA replication and enhanced expression of a gene located in the same chromosomal domain is observed. Reversion of aberrant DNA replication and reduction of c-myc expression to normal in hybrid cells may be due to a site-specific trans effect which overrides the control brought about in cis by retroviral insertion near the c-myc gene.
T淋巴瘤细胞与淋巴细胞之间的种内体细胞杂种具有高度致瘤性，而T淋巴瘤细胞与正常成纤维细胞融合则会导致杂种细胞的致瘤性降低甚至完全被抑制。一种特殊的细胞遗传学现象定义了这两类杂种。通过溴脱氧尿苷脉冲标记进行的DNA复制分析显示，肿瘤细胞和高度致瘤性杂种细胞的c-myc染色体区域存在异常条带模式。在致瘤性被抑制的杂种细胞中，来自肿瘤亲本的染色体已恢复为正常的DNA复制条带。肿瘤细胞和高度致瘤性杂种细胞中的异常DNA复制与c-myc表达增强一致。在致瘤性被抑制且具有正常DNA复制条带的杂种细胞中，c-myc表达也降低。因此，观察到异常DNA复制与位于同一染色体区域的基因表达增强之间存在相关性。杂种细胞中异常DNA复制的恢复和c-myc表达降至正常可能是由于一种位点特异性反式效应，该效应超越了由c-myc基因附近的逆转录病毒插入在顺式中所带来的控制。
