Maruyama K, Fukushima T, Mochizuki S, Kawamura K, Koshikawa N, Miyauchi M, Nakano M
Chiba Cancer Center Research Institute, Japan.
Leukemia. 1994 Apr;8 Suppl 1:S36-40.
To elucidate the role of HTLV-I in human neoplasia, DNA was extracted from tumor tissues, cultured cells, and/or sera from 20 HTLV-I seropositive and from 10 seronegative cancer patients, subjected to PCR-PAGE, and analyzed by Southern hybridization. HTLV-I related sequences were detected in tumors of the seropositives with different types of cancer. In the seronegatives, gag related sequences were detected in some tumors, whereas LTR related sequences were detected in only uterus carcinoma and tax related sequences in none of tumors examined. These sequences were detected in tumor cells as well as lymphoid cells by in situ hybridization. Some of these sequences were also detected in cultured fibroblasts derived from ATL patients. Cultured normal human lymphocytes grew continuously in conditioned media following HTLV-I infection, and transformed on exposure to carcinogens. Chromosome changes in transformed cells appeared clustering to chromosomes abnormalized on HTLV-I infection. The frequency of abnormal chromosomes in lymphocytes was significantly higher in the seropositives and in their family members than in seronegative normal donors. The frequency increased with advancement of host age in the seropositives but not in the seronegatives. These findings indicate that some individuals carry HTLV-I related sequences that may be derepressed by host aging and resulted in increasing genetic instability of host cells rendering them increasingly susceptible to carcinogens.
为阐明人类T细胞白血病病毒I型（HTLV-I）在人类肿瘤形成中的作用，从20例HTLV-I血清阳性和10例血清阴性癌症患者的肿瘤组织、培养细胞和/或血清中提取DNA，进行聚合酶链反应-聚丙烯酰胺凝胶电泳（PCR-PAGE），并通过Southern杂交分析。在不同类型癌症的血清阳性患者的肿瘤中检测到HTLV-I相关序列。在血清阴性患者中，在一些肿瘤中检测到gag相关序列，而仅在子宫癌中检测到LTR相关序列，在所检查的肿瘤中均未检测到tax相关序列。通过原位杂交在肿瘤细胞以及淋巴细胞中检测到这些序列。在源自成人T细胞白血病（ATL）患者的培养成纤维细胞中也检测到其中一些序列。感染HTLV-I后，培养的正常人淋巴细胞在条件培养基中持续生长，并在接触致癌物后发生转化。转化细胞中的染色体变化似乎聚集在HTLV-I感染时异常的染色体上。血清阳性患者及其家庭成员淋巴细胞中异常染色体的频率显著高于血清阴性正常供体。在血清阳性患者中，异常染色体的频率随宿主年龄增长而增加，而在血清阴性患者中则不然。这些发现表明，一些个体携带HTLV-I相关序列，这些序列可能因宿主衰老而解除抑制，导致宿主细胞遗传不稳定性增加，使其对致癌物越来越敏感。
