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高剂量聚肌苷酸-聚胞苷酸诱导的小鼠L细胞干扰素对BALB/c小鼠中劳斯氏白血病病毒诱导的红白血病的影响。

The effect of high doses of poly(I).poly(C) induced mouse L cell interferon on Rauscher leukemia virus induced erythroleukemia in BALB/c mice.

作者信息

Hekman R A, Prins M E, Bosveld I J, Trapman J

出版信息

Int J Cancer. 1981;27(4):493-500. doi: 10.1002/ijc.2910270412.

Abstract

The effect of high doses of poly(I).poly(C) induced mouse L-cell interferon on the development of Rauscher murine leukemia virus (R-MuLV)-induced erythroleukemia in BALB/c mice was determined. Female mice, 4 to 5 weeks old, were infected with R-MuLV and treated with interferon every 24 h starting 6 h after virus inoculation. Under these conditions injection of 3-5 X 10(4) units of interferon caused a partial inhibition of the leukemia process. Daily application of 3 X 10(5) units completely or almost completely inhibited the erythroleukemia. After 14 days of treatment with these high doses of interferon, spleen weights of interferon-treated infected mice were comparable to those of uninfected animals which received only interferon. Also, no Rauscher cells in spleens and livers of R-MuLV-infected interferon-treated infected animals could be demonstrated and the spleen structure was well preserved in these mice. In interferon-treated infected animals no virus could be detected in the serum as judged from the absence of reverse transcriptase activity in the serum. Moreover, no virus-infected cells could be demonstrated in spleen or liver as deduced from negative immunofluorescence data using anti-p30 and anti-gp70 sera. No virions budding from spleen cell membranes were seen by electron microscopic studies. However, when interferon treatment was stopped the leukemic process was reactivated and all the mice died. In control experiments interferon caused an inhibition of red blood cell formation and a 50 to 100% enlargement of the spleen. Pharmacokinetic data showed that, after intraperitoneal inoculation, maximum amounts of interferon were present in the peripheral blood after 1-2 h. After 12-24 h almost all interferon activity had disappeared from the blood.

摘要

测定了高剂量的聚肌苷酸-聚胞苷酸(poly(I).poly(C))诱导的小鼠L细胞干扰素对BALB/c小鼠中劳斯氏鼠白血病病毒(R-MuLV)诱导的红白血病发展的影响。4至5周龄的雌性小鼠感染R-MuLV,并在病毒接种后6小时开始每24小时用干扰素治疗一次。在这些条件下,注射3 - 5×10⁴单位的干扰素会部分抑制白血病进程。每天应用3×10⁵单位可完全或几乎完全抑制红白血病。用这些高剂量干扰素治疗14天后,接受干扰素治疗的感染小鼠的脾脏重量与仅接受干扰素的未感染动物相当。此外,在接受R-MuLV感染并经干扰素治疗的动物的脾脏和肝脏中未检测到劳斯氏细胞,并且这些小鼠的脾脏结构保存良好。在接受干扰素治疗的感染动物的血清中未检测到病毒,这是根据血清中逆转录酶活性的缺失判断的。此外,根据使用抗p30和抗gp70血清的阴性免疫荧光数据推断,在脾脏或肝脏中未发现病毒感染细胞。电子显微镜研究未观察到从脾细胞膜出芽的病毒粒子。然而,当停止干扰素治疗时,白血病进程重新激活,所有小鼠死亡。在对照实验中,干扰素会抑制红细胞生成并使脾脏肿大50%至100%。药代动力学数据表明,腹腔接种后,1 - 2小时外周血中干扰素含量最高。12 - 24小时后,血液中几乎所有的干扰素活性都消失了。

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