Ershler Maxim A, Nifontova Irina N, Olshanskaya Yulia V, Todria Tamara V, Chertkov Joseph L, Drize Nina J
Hematological Scientific Center, Moscow, Russia.
Hematol J. 2003;4(1):74-7. doi: 10.1038/sj.thj.6200203.
Total cell production and longevity of hematopoiesis in long-term bone marrow culture of tumor necrosis factor (TNF)-deficient mice (LTBM-TNFko) are increased. The rate of apoptosis is decreased during the first 40 weeks in culture, then the level of apoptosis reaches levels of wild-type cultures. Extended lifespan of primary cultures usually is the consequence of the neoplastic transformation. We set out to check this possibility in the LTBM-TNFko. Telomerase activity in suspension fraction (SF) of LTBM-TNFko increases with time and reaches maximum a year after culture initiation. Cytogenetic study reveals genome instability in SF and hyperploidy in the adhesion cell layer (ACL) of LTBM-TNFko. All of the above indicate the possibility of neoplastic transformation. However, histological study of cells and CFU-S-derived colonies of SF does not reveal a block of differentiation. Cells of SF are unable to grow without ACL. Although those cells could proliferate in the presence of exogenous growth factors, they are not able to be passaged. Attempts of passaging ACL cells failed as well. Neither healthy nor sublethally irradiated recipients injected intravenously or intraperitoneally with cells of SF develop tumors within 8 months of observation. In conclusion, abnormal dynamics of long-term bone marrow culture of TNF-deficient mice could not be explained by neoplastic transformation.
肿瘤坏死因子（TNF）缺陷小鼠的长期骨髓培养（LTBM-TNFko）中，总细胞产量和造血寿命增加。培养的前40周细胞凋亡率降低，之后凋亡水平达到野生型培养物的水平。原代培养物寿命延长通常是肿瘤转化的结果。我们着手在LTBM-TNFko中验证这种可能性。LTBM-TNFko悬浮部分（SF）的端粒酶活性随时间增加，培养开始一年后达到最大值。细胞遗传学研究揭示了LTBM-TNFko的SF中基因组不稳定以及黏附细胞层（ACL）中超倍体现象。上述所有情况表明存在肿瘤转化的可能性。然而，对SF的细胞和CFU-S衍生集落进行组织学研究未发现分化阻滞。SF的细胞在没有ACL的情况下无法生长。尽管这些细胞在外源生长因子存在时能够增殖，但它们无法传代。对ACL细胞进行传代的尝试也失败了。在8个月的观察期内，无论是健康的还是接受亚致死剂量照射的受体，经静脉或腹腔注射SF细胞后均未发生肿瘤。总之，TNF缺陷小鼠长期骨髓培养的异常动态不能用肿瘤转化来解释。
