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I型人类T细胞白血病病毒作为感染人类淋巴细胞时诱导基因变化的病原体。

Human T-cell leukemia virus type I as agent inducing genetic changes in infected human lymphocytes.

作者信息

Maruyama K, Fukushima T, Mochizuki S, Kawamura K, Miyauchi M

机构信息

Department of Pathology, Chiba Cancer Center Research Institute, Japan.

出版信息

Leukemia. 1992;6 Suppl 3:60S-63S.

PMID:1602828
Abstract

Sera and DNA samples, including cord blood, were examined from six members of a three-generation family suspected of being carriers of HTLV-I. Serum antibodies to HTLV-I were detected by Western blot analysis more clearly in adults than in children. DNA sequences related to HTLV-I-gag and -tax, but not -pol genes were detected more clearly in specific PCR products of DNA of adults than those of children, and of the cord blood by Southern hybridization analysis. HTLV-I-related DNA sequences were also detected in some HTLV-I-seropositive as well as seronegative patients with T-cell dyscrasia and with other diseases, including carcinoma. Frequencies of chromosome abnormalities were found to be significantly higher in lymphocytes of HTLV-I-seropositive persons than in those of HTLV-I-seronegative persons. Immortalization of cultured lymphocytes following infection with HTLV-I was found to be accompanied by chromosome and gene rearrangements. Transformation of these cells following treatment with carcinogens was found to be accompanied by additional chromosome rearrangements. These results suggest that some persons may be born with HTLV-I-related sequences that are repressed in childhood. Repeated expression of their products may result not only in the host antibody response but also in increased chromosomal instability and in increased risk for further genetic changes of carrier cells when exposed to environmental carcinogens.

摘要

对一个疑似HTLV-I携带者的三代家族的六名成员的血清和DNA样本(包括脐带血)进行了检测。通过蛋白质印迹分析检测到,成人血清中针对HTLV-I的抗体比儿童更清晰。通过Southern杂交分析,在成人DNA的特定PCR产物中比在儿童及脐带血的DNA中更清晰地检测到与HTLV-I的gag和tax基因相关但与pol基因无关的DNA序列。在一些患有T细胞发育异常以及包括癌症在内的其他疾病的HTLV-I血清阳性和血清阴性患者中也检测到了HTLV-I相关的DNA序列。发现HTLV-I血清阳性者淋巴细胞中的染色体异常频率明显高于HTLV-I血清阴性者。发现感染HTLV-I后培养的淋巴细胞永生化伴随着染色体和基因重排。在用致癌物处理后这些细胞的转化伴随着额外的染色体重排。这些结果表明,一些人可能天生带有在儿童期受到抑制的HTLV-I相关序列。其产物的反复表达可能不仅导致宿主抗体反应,还会增加染色体不稳定性,并在暴露于环境致癌物时增加携带细胞进一步发生基因变化的风险。

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