Fundia A F, Slavutsky I R, Larripa I B
Sección Citogenética, Academia Nacional de Medicina, Buenos Aires, Argentina.
Sangre (Barc). 1990 Feb;35(1):4-9.
Fragile sites are specific chromosomal sites prone to breakage and rearrangements and they are probably related with cancer development. Fragile sites expression induced by 5-fluorodeoxyuridine (FudR) or 5-bromodeoxyuridine (BrdU) was analyzed in 4 healthy individuals and 4 patients affected with lymphoproliferative disorders: one Hodgkin's disease, one mycosis fungoides and two chronic lymphoproliferative disorders. Three standard peripheral lymphocyte cultures with F-10 medium and 5% of fetal calf serum were set up for each individual. For fragile sites induction, 10 micrograms/mL FudR or 50 micrograms/mL BrdU were added 24 hr or 6 hr before harvest. Standard and sequential G banded metaphases were studied for each individual and treatment. Quantitative analysis showed a low incidence of acentric fragments, dicentric, tri- or quadriradials, while gaps and breaks were more frequently observed. Chromosome or chromatid type aberrations were compared, showing similar values in all non-treated cultures. Chromosome type aberrations were increased in patients and controls treated cultures. Patient cultures treated by FudR presented a threefold increase of chromosome type alterations respect to chromatid ones. Moreover, chromosome breaks showed a twofold increase in patient treated cultures respect to control ones. The high number of chromosome breaks detected in these cases could be associated with an increased chromosome instability in cancer patients. Twenty common fragile sites (c-fra) were identified with sequential G banding. Patients and controls individuals have expressed 14 c-fra. Eleven of them were induced, in different proportions, by both chemical agents, showing that fragile sites share a structural homology in DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
脆性位点是特定的染色体位点,易于发生断裂和重排,可能与癌症发展相关。在4名健康个体和4名患有淋巴增殖性疾病的患者中分析了由5-氟脱氧尿苷(FudR)或5-溴脱氧尿苷(BrdU)诱导的脆性位点表达情况:1例霍奇金病、1例蕈样肉芽肿病和2例慢性淋巴增殖性疾病。为每个个体建立了3个含有F-10培养基和5%胎牛血清的标准外周淋巴细胞培养体系。为诱导脆性位点,在收获前24小时或6小时添加10微克/毫升FudR或50微克/毫升BrdU。对每个个体和处理进行标准和连续G带中期分析。定量分析显示无着丝粒片段、双着丝粒、三或四射体的发生率较低,而间隙和断裂更常被观察到。比较了染色体或染色单体型畸变,在所有未处理的培养物中显示出相似的值。在患者和对照处理的培养物中染色体型畸变增加。用FudR处理的患者培养物中染色体型改变相对于染色单体型增加了三倍。此外,患者处理的培养物中染色体断裂相对于对照增加了两倍。在这些病例中检测到的大量染色体断裂可能与癌症患者染色体不稳定性增加有关。通过连续G带鉴定出20个常见脆性位点(c-fra)。患者和对照个体表达了14个c-fra。其中11个由两种化学试剂以不同比例诱导,表明脆性位点在DNA中具有结构同源性。(摘要截断于250字)