Thymocyte injury after in vitro chemical exposure: potential mechanisms for thymic atrophy.
Thymocyte injury after in vitro chemical exposure: potential mechanisms for thymic atrophy.
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体外化学暴露后胸腺细胞损伤：胸腺萎缩的潜在机制。
DOI：
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发表时间：
1992
影响因子：
3.5
通讯作者：
M. I. Luster
中科院分区：
文献类型：
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作者：
C. Comment;B. Blaylock;D. Germolec;P. Pollock;Y. Kouchi;H. Brown;Gary J. Rosenthal;M. I. Luster
除了肝损伤外，胸腺萎缩是啮齿动物亚慢性毒性研究中的常见观察结果。我们已经检查了在啮齿动物中产生胸腺萎缩的代表性化学物质导致直接胸腺细胞损伤的能力，因为这些作用的机制尚未确定。虽然一些化合物检查没有任何可观察到的直接影响胸腺细胞，其他抑制淋巴细胞增殖或启动细胞死亡。在后一组中，胸腺细胞死亡之前总是增加细胞内Ca++和参与，在不同程度上，坏死和凋亡事件。细胞凋亡，证明细胞DNA裂解成180-200碱基对寡核苷酸的倍数和放线菌酮处理的部分细胞保护，是最明显的乙醛或二丁基二氯化锡处理后。许多产生胸腺萎缩的化合物也抑制T淋巴细胞增殖，而没有细胞死亡的证据。考虑到许多测试的化合物未能产生任何直接胸腺细胞损伤的证据（即，坏死、细胞凋亡或细胞增殖抑制），间接机制也可能参与胸腺萎缩，并可能靶向骨髓中的原胸腺细胞，在正常归巢模式后或损伤胸腺上皮。因此，似乎有多种机制可能是化学诱导的胸腺萎缩和/或损伤的原因。
In addition to hepatic injury, thymic atrophy is a common observation in rodent subchronic toxicity studies. We have examined representative chemicals which produce thymic atrophy in rodents for their ability to cause direct thymocyte injury because the mechanism(s) responsible for these effects have not been determined. Although a number of the compounds examined failed to have any observable direct effect on thymocytes, others either inhibited lymphocyte proliferation or initiated cell death. In the latter group, thymocyte death was always preceded by increases in intracellular Ca++ and involved, to varying degrees, necrotic and apoptotic events. Apoptosis, as evidenced by cellular DNA cleavage into multiples of 180-200-base pair oligonucleotides and partial cell protection by cycloheximide treatment, was most evident after treatment with acetaldehyde or dibutyltin dichloride. A number of compounds that produce thymic atrophy also inhibited T lymphocyte proliferation without evidence of cell death. Considering that many of the compounds tested failed to produce any evidence of direct thymocyte injury (i.e., necrosis, apoptosis or inhibition of cell proliferation), indirect mechanisms may also be involved in thymic atrophy and may target prothymocytes in the bone marrow, after normal homing patterns or injure the thymic epithelium. Thus, it appears that a variety of mechanisms may be responsible for chemical-induced thymic atrophy and/or injury.