Borden E C, Carter W A, Sensenbrenner L L, Owens A H, Lichtenstein J, Gray G D, Neil G L, Nichol F R, Li L H
Int J Cancer. 1974 Dec 15;14(6):817-25. doi: 10.1002/ijc.2910140616.
Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25-50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv was measurable in plasma for up to 6 h. SvC, at 300 mg/kg/day, reduced mean spleen weight of infected mice from 478 plus or minus 51 (SE) mg to 300 plus or minus 55 (SE) mg. Rifampicin, at 250 mg/kg/day, had no similar activity. Decrease in caloric intake and in body-weight gain also resulted in an inhibition of RLV splenomegaly; although Sv-treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to control group, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (1) Splenomegaly and mortality, induced by L1210 or a non-infective transplantable tumor of RLV origin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interferon production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RLV splenomegaly by Sv.
链黑菌素(Sv)是一种蒽环类大环内酯抗生素,可使劳氏白血病病毒(RLV)引起的脾肿大缩小25%至50%。所有测试的链黑菌素在从感染到处死期间通过随意采食或插管口服给药时均有效。通过插管给药时,血浆中的链黑菌素在长达6小时内均可检测到。链黑菌素C以300毫克/千克/天的剂量给药,可使感染小鼠的平均脾脏重量从478±51(标准误)毫克降至300±55(标准误)毫克。利福平以250毫克/千克/天的剂量给药则无类似活性。热量摄入和体重增加的减少也会抑制RLV引起的脾肿大;虽然用链黑菌素治疗的小鼠体重增加,但增加幅度通常略低于对照组。然而,在感染前一周用含链黑菌素的饲料喂养的小鼠,在最初体重减轻一段时间后,体重增加速度与对照组相当,处死时脾肿大明显减轻。几项观察结果提示了链黑菌素的选择性和对病毒事件的特异性:(1)由L1210或RLV来源的非感染性可移植肿瘤诱导的脾肿大和死亡率未受到抑制。(2)未观察到对正常造血脾集落的抑制作用。(3)宿主免疫反应,包括细胞免疫和体液免疫以及干扰素的产生和作用,均未受到抑制。因此,尽管体重和摄入量略有下降的影响尚不能明确确定,但这些发现最符合链黑菌素对RLV脾肿大的选择性抑制作用。