MYCOPLASMAS AND ONCOGENESIS - PERSISTENT INFECTION AND MULTISTAGE MALIGNANT TRANSFORMATION
MYCOPLASMAS AND ONCOGENESIS - PERSISTENT INFECTION AND MULTISTAGE MALIGNANT TRANSFORMATION
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DOI：
10.1073/pnas.92.22.10197
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发表时间：
1995-10-24
影响因子：
11.1
通讯作者：
LO, SC
中科院分区：
文献类型：
--
作者：
TSAI, S;WEAR, DJ;LO, SC
使用培养的小鼠胚胎细胞C3 H/10 T1/2（C3 H）研究了人支原体的致癌潜力。对发酵支原体和穿透支原体（在艾滋病患者中发现频率异常高的支原体）进行了检查。与急性转化相反，恶性细胞转化的促进和进展是一个多阶段的过程，具有长潜伏期。发酵支原体感染后，C3 H细胞表现出恶性特征的表型变化，随着感染时间的延长，恶性特征逐渐变得更加突出。至少在第11代之前，如果通过抗生素治疗根除支原体，则所有恶性变化都是可逆的，进一步持续感染支原体直到18代，导致不可逆的转化形式，包括在动物中形成肿瘤的能力和高表达的能力。软琼脂克隆效率尽管在可逆阶段期间被任一支原体感染的C3 H细胞中的染色体丢失和易位变化并不显著，但转化的不可逆阶段的开始与这种核型改变一致，遗传不稳定性-即，永久转化细胞的显著染色体改变--很可能是由负责DNA复制或修复保真度的基因突变引起的。一旦诱导，染色体改变在培养细胞和动物中继续积累，而没有转化微生物的持续存在。
Oncogenic potential of human mycoplasmas was studied using cultured mouse embryo cells, C3H/10T1/2 (C3H). Mycoplasma fermentans and Mycoplasma penetrans, mycoplasmas found in unusually high frequencies among patients with AIDS, were examined. Instead of acute transformation, a multistage process in promotion and progression of malignant cell transformation with long latency was noted; after 6 passages (1 wk per passage) of persistent infection with M. fermentans, C3H cells exhibited phenotypic changes with malignant characteristics that became progressively more prominent with further prolonged infection, Up to at least the 11th passage, all malignant changes were reversible if mycoplasmas were eradicated by antibiotic treatment, Further persistent infection with the mycoplasmas until 18 passages resulted in an irreversible form of transformation that included the ability to form tumors in animals and high soft agar cloning efficiency, Whereas chromosomal loss and translocational changes in C3H cells infected by either mycoplasma during the reversible stage were not prominent, the onset of the irreversible phase of transformation coincided with such karyotypic alteration, Genetic instability-i.e., prominent chromosomal alteration of permanently transformed cells-was most likely caused by mutation of a gene(s) responsible for fidelity of DNA replication or repair, Once induced, chromosomal alterations continued to accumulate both in cultured cells and in animals without the continued presence of the transforming microbes, Mycoplasma-mediated multistage oncogenesis exhibited here shares many characteristics found in the development of human cancer.