TUMOR NECROSIS FACTOR STIMULATES DNA-SYNTHESIS IN THE LIVER OF INTACT RATS

TUMOR NECROSIS FACTOR STIMULATES DNA-SYNTHESIS IN THE LIVER OF INTACT RATS
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DOI:
10.1016/s0006-291x(88)81134-3
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发表时间:
1988-06-16
影响因子:
3.1
通讯作者:
DOVALE, HG
DOVALE, HG
中科院分区:
生物学4区
文献类型:
--
作者:
FEINGOLD, KR;SOUED, M;DOVALE, HG

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肿瘤坏死因子对肿瘤细胞株具有细胞毒作用,但可促进某些未转化细胞的生长。由于注射肿瘤坏死因子的动物肝脏体积增大,我们研究了正常大鼠肝脏DNA的[~3H]胸腺嘧啶核苷掺入。肿瘤坏死因子注射后20小时,[~3H]胸腺嘧啶核苷掺入显著增加,24小时达到高峰。增加DNA合成的最低剂量为10微克/200克大鼠,最大剂量为25微克/200克,大大低于最大限度增加血浆甘油三酯所需的剂量。[~3H]胸腺嘧啶核苷掺入的增加是由于DNA聚合酶α活性的增加(与DNA复制有关),而不是DNA聚合酶β活性(与DNA修复有关)加伽马活性。这些结果表明,给予肿瘤坏死因子可刺激完整动物肝脏中的DNA复制。
TNF is cytotoxic to tumor cell lines but enhances growth of some nontransformed cells. Because animals administered TNF have an increase in liver size, we studied the [3H]thymidine incorporation into DNA in the liver of intact rats. A significant increase in [3H]thymidine incorporation is seen 20 hours following TNF administration and peaks at 24 hours. The lowest dose of TNF that increases DNA synthesis is 10 .mu.g/200 g rat with a maximal increase occurring with 25 .mu.g/200 g, considerably less than the dose required for maximally increasing plasma triglycerides. The increase in [3H]thymidine incorporation was shown to be due to an increase in DNA polymerase alpha activity (associated with the replication of DNA) rather than DNA polymerases beta (associated with DNA repair) plus gamma activity. These results indicate that TNF administration stimulates DNA replication in the liver of intact animals.