Aggarwal B B, Gadhia P K, Hopwood V L, Dave B J, Risin S, Owen-Schaub L, Pandita R, Pathak S
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Lymphokine Cytokine Res. 1993 Feb;12(1):9-19.
We have previously reported the isolation of the cytotoxic factors, tumor necrosis factor-alpha (TNF-alpha), from monocytes and lymphotoxin or TNF-beta, from an established human B lymphoblastoid cell line. In the current study, we examined the production of cytotoxic factors by primary lymphoid cells derived from patients with different malignancies and correlated it with the chromosomal abnormalities in producer cells. Lymphoid cell lines were established from 78 untreated patients with breast carcinoma, 2 with cervical carcinoma, 24 with colon carcinoma, 12 with prostate carcinoma, 3 with melanoma, and the remaining from asymptomatic family members. Lymphoid cells from all 119 patients and their asymptomatic family members constitutively produced as much as 240 units/ml of TNF-beta in vitro. In contrast, TNF-alpha was produced by lymphoid cells from only 6 patients; a related cytokine with similar biological properties to TNF-beta. Sixty-five of these 119 samples were also analyzed for chromosomal abnormalities by standard cytogenetic technique. The production of TNFs was accompanied with varying degrees of chromosomal abnormalities in the cells from all patients. These included both structural and numerical abnormalities. We also examined the direct effect of TNF-beta on the induction of chromosomal abnormalities in growing cultures of both T and B lymphocytes. Our preliminary results indicate that treatment of lymphocytes with this cytokine induced chromosomal rearrangements in a dose-dependent manner. Thus, we provide for the first time both indirect and direct evidence that a soluble mediator such as TNF-beta can induce chromosomal alterations commonly associated with different types of tumors.
我们之前报道过从单核细胞中分离出细胞毒性因子肿瘤坏死因子-α（TNF-α），以及从一个已建立的人B淋巴母细胞系中分离出淋巴毒素或TNF-β。在当前研究中，我们检测了来自不同恶性肿瘤患者的原代淋巴细胞产生细胞毒性因子的情况，并将其与产生细胞中的染色体异常相关联。从78例未经治疗的乳腺癌患者、2例宫颈癌患者、24例结肠癌患者、12例前列腺癌患者、3例黑色素瘤患者以及其余无症状家庭成员中建立了淋巴细胞系。来自所有119例患者及其无症状家庭成员的淋巴细胞在体外组成性地产生高达240单位/毫升的TNF-β。相比之下，只有6例患者的淋巴细胞产生TNF-α；一种与TNF-β具有相似生物学特性的相关细胞因子。还通过标准细胞遗传学技术对这119个样本中的65个进行了染色体异常分析。所有患者细胞中TNF的产生都伴随着不同程度的染色体异常。这些异常包括结构和数量异常。我们还检测了TNF-β对T和B淋巴细胞生长培养物中染色体异常诱导的直接作用。我们的初步结果表明，用这种细胞因子处理淋巴细胞会以剂量依赖的方式诱导染色体重排。因此，我们首次提供了间接和直接证据，证明可溶性介质如TNF-β可诱导通常与不同类型肿瘤相关的染色体改变。
