Ribeiro R C, Douglass E C, Williams D L, Raimondi S C, Valentine M, Lewis S, Crist W M
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Leuk Lymphoma. 1992 Aug;7(5-6):401-7. doi: 10.3109/10428199209049795.
Many fragile sites in the human genome occur at or near chromosomal breakpoints reportedly involved in translocations of DNA material in neoplastic cells. This fact has led some investigators to postulate that fragile sites have a pathogenic role in human neoplasia. To learn whether caffeine-induced fragile sites relate to breakpoints found in the neoplastic cells of an individual patient, we studied lymphocytes from the peripheral blood of 32 patients in remission from malignant disease. Lymphocytes were cultured in medium containing either 5-Fluoro-2'-deoxyuridine (FdU) or FdU plus caffeine, and G-banded metaphases were examined for nonrandom breaks. Analyses of completely G-banded malignant cell chromosomes from 31 of the 32 patients were available for comparison. In only once case, a 5-year-old child with acute lymphoblastic leukemia, did a caffeine-induced fragile site (1q44) coincide with a breakpoint in the neoplastic cells [dup(1)(q21-->q44)]. Our findings suggest that chromosomal abnormalities in childhood malignancies cannot generally be explained by the presence of FdU- or FdU plus caffeine-induced fragile sites.
据报道，人类基因组中的许多脆性位点出现在染色体断点处或其附近，这些断点与肿瘤细胞中DNA物质的易位有关。这一事实使得一些研究人员推测脆性位点在人类肿瘤形成中具有致病作用。为了了解咖啡因诱导的脆性位点是否与个体患者肿瘤细胞中发现的断点相关，我们研究了32例恶性疾病缓解期患者外周血中的淋巴细胞。淋巴细胞在含有5-氟-2'-脱氧尿苷（FdU）或FdU加咖啡因的培养基中培养，并检查G带中期相有无非随机断裂。对32例患者中31例患者的完全G带恶性细胞染色体进行了分析以供比较。仅在1例5岁急性淋巴细胞白血病患儿中，咖啡因诱导的脆性位点（1q44）与肿瘤细胞中的一个断点[dup(1)(q21-->q44)]重合。我们的研究结果表明，儿童恶性肿瘤中的染色体异常通常不能用FdU或FdU加咖啡因诱导的脆性位点来解释。
