Frías S, Molina B, Gómez L, Carnevale A
Departamento de Investigación en Genética Humana, Instituto Nacional de Pediatría, México, D.F.
Rev Invest Clin. 1992 Oct-Dec;44(4):519-24.
It has been shown that the addition of normal plasma to Fanconi anemia (FA) lymphocyte cultures significantly decreases the frequency of mitomycin C (MMC) induced chromosome aberrations, suggesting that normal plasma contains a diffusible correction factor (CF) which is able to partially complement FA lymphocytes. On the other hand, there is evidence suggesting that FA cells are defective in the DNA postreplicative repair. CF could then be involved in DNA repair processes and in possible inducible mechanisms. In the present study MMC-treated FA lymphocytes were grown during the last 24 hours of culture, in conditioned media obtained from untreated and MMC-treated normal cells. The purpose was to investigate if MMC-stressed normal cells were induced to produce CF in vitro. The results failed to show a constant decrease of FA cells chromosome aberrations when plasma-free conditioned media from MMC-stressed normal cells were added (experiments 2 and 3). However, when the conditioned media were supplemented with normal plasma (experiments 1 and 4) a partial repair of MMC-induced damage of the FA cells was observed. The results suggest the presence of CF in normal plasma and two possible mechanisms of action are suggested: CF is involved in DNA repair of MMC-damaged FA cells or it induces cellular division selecting the less damaged cell population through mitosis.
研究表明,向范可尼贫血(FA)淋巴细胞培养物中添加正常血浆可显著降低丝裂霉素C(MMC)诱导的染色体畸变频率,这表明正常血浆中含有一种可扩散的校正因子(CF),它能够部分补充FA淋巴细胞。另一方面,有证据表明FA细胞在DNA复制后修复方面存在缺陷。CF可能参与DNA修复过程以及可能的诱导机制。在本研究中,经MMC处理的FA淋巴细胞在培养的最后24小时,在从未经处理和经MMC处理的正常细胞获得的条件培养基中生长。目的是研究经MMC应激的正常细胞是否在体外被诱导产生CF。当添加来自经MMC应激的正常细胞的无血浆条件培养基时,结果未能显示FA细胞染色体畸变持续减少(实验2和3)。然而,当条件培养基补充正常血浆时(实验1和4),观察到FA细胞的MMC诱导损伤得到部分修复。结果表明正常血浆中存在CF,并提出了两种可能的作用机制:CF参与MMC损伤的FA细胞的DNA修复,或者它通过有丝分裂诱导细胞分裂,选择损伤较小的细胞群体。