Floersheim G L
Eur J Cancer Clin Oncol. 1982 Aug;18(8):777-84. doi: 10.1016/0277-5379(82)90077-3.
A lethal dose of the cytotoxic agent dimethyl-myleran (DMM) is survived by 75-100% of mice reinfused with autologous bone marrow. In mice inoculated beforehand with a syngeneic Moloney lymphoma and then treated with lethal DMM, hemopoietic restoration and survival are compromised. With subcutaneous tumour challenge, in the face of substantial early toxicity, a therapeutic effect of DMM prevails. With intravenous or intraperitoneal tumour challenge the restorative potency of the autograft and thus the therapeutic drug effect are lost since practically all animals die from DMM. The reduced tolerance of mice carrying the Moloney lymphoma applies more generally to cytotoxic measures. The toxicity from sublethal doses of DMM, cyclophosphamide (CY) and total-body irradiation (TBI) is increased in mice inoculated subcutaneously shortly before with the lymphoma cells. The LD50 of the three agents is reduced by up to 70% according to the number of injected tumour cells or the time allowed for their multiplication. The effect is also provided by a cell-free tumour filtrate. Since the filtrate reduces bone marrow cellularity, the decreased tolerance could be due to the impairment of hemopoiesis by a tumour factor. Two human cancers growing as xenografts in immunosuppressed mice did not increase the sensitivity to DMM.
细胞毒性药物二甲磺酸丁酯（DMM）的致死剂量，可被75%至100%接受自体骨髓再输注的小鼠耐受。预先接种同基因莫洛尼淋巴瘤然后用致死剂量DMM治疗的小鼠，造血恢复和存活率会受到影响。在皮下接种肿瘤的情况下，尽管早期毒性很大，但DMM的治疗效果占主导。在静脉或腹腔接种肿瘤的情况下，自体移植的恢复能力以及治疗药物的效果丧失，因为几乎所有动物都死于DMM。携带莫洛尼淋巴瘤的小鼠耐受性降低，这更普遍地适用于细胞毒性措施。在皮下接种淋巴瘤细胞后不久的小鼠中，亚致死剂量的DMM、环磷酰胺（CY）和全身照射（TBI）的毒性增加。根据注射的肿瘤细胞数量或其增殖时间，这三种药物的半数致死剂量（LD50）可降低多达70%。无细胞肿瘤滤液也有同样的效果。由于该滤液会降低骨髓细胞数量，耐受性降低可能是由于肿瘤因子对造血功能的损害所致。在免疫抑制小鼠中作为异种移植生长的两种人类癌症，并未增加对DMM的敏感性。
