Zhuang W, Tajima S, Okada K, Ikawa Y, Aida Y
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Leukemia. 1997 Apr;11 Suppl 3:344-6.
To elucidate the mechanism of leukemogenesis induced by bovine leukemia virus (BLV), the abnormality of p53 tumor suppressor gene was examined using the sequencing method of polymerase chain reaction (PCR)-amplified DNA from peripheral blood lymphocytes (PBL) and tumors from BLV-infected cattle that showed evidence of different stages during the progression of enzootic bovine leukosis (EBL). Mutations of the p53 gene were found in tumor cells from cattle with EBL, but not in PBL from BLV-free normal cattle or BLV-infected cattle without any evidence of tumor, suggesting mutation of p53 gene occurred specifically at the lymphoma stage of the disease. Twelve of eighteen cattle with EBL had seven missense and five silent mutations. The mutations were mapped to the highly evolutionarily conserved regions of p53 gene, and were involved in the DNA binding of p53. Thus, it appeared that the p53 point mutation is one of the critical events leading from the asymptomatic stage to the lymphoma stage.
为阐明牛白血病病毒（BLV）诱导白血病发生的机制，采用聚合酶链反应（PCR）测序法，检测了感染BLV的牛外周血淋巴细胞（PBL）及肿瘤组织中p53肿瘤抑制基因的异常情况，这些牛在地方流行性牛白血病（EBL）进展过程中表现出不同阶段的特征。在患有EBL的牛的肿瘤细胞中发现了p53基因的突变，但在无BLV的正常牛或无任何肿瘤迹象的感染BLV的牛的PBL中未发现，这表明p53基因的突变在疾病的淋巴瘤阶段特异性发生。18头患有EBL的牛中有12头出现了7个错义突变和5个沉默突变。这些突变定位于p53基因高度进化保守区域，且与p53的DNA结合有关。因此，p53点突变似乎是从无症状阶段发展到淋巴瘤阶段的关键事件之一。
