Schmalbach T K, Borch R F
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, New York 14642.
Cancer Res. 1989 May 15;49(10):2574-7.
The effect of diethyldithiocarbamate (DDTC) on myelotoxicity induced by 1,3-bis(2-chloroethyl)-1-nitrosourea, Adriamycin, or mitomycin C in C57BL/6J x DBA/2J mice is reported here. All drugs were administered i.v. Myelotoxicity was assessed, 24 h after administration of the myelotoxic drug, using bone marrow stem cell (spleen colony-forming unit) and granulocyte/macrophage progenitor cell (granulocyte/macrophage colony-forming unit in culture) clonogenic assays. Administration of DDTC alone had no effect on spleen colony-forming units or granulocyte/macrophage colony-forming units in culture. 1,3-Bis(2-chloroethyl)-1-nitrosourea showed a dose-dependent toxicity for both cell types, and subsequent treatment with DDTC (300 mg/kg i.v. 3 h after 1,3-bis(2-chloroethyl)-1-nitrosourea) ameliorated this toxicity. The same dosing regimen of DDTC ameliorated Adriamycin-induced toxicity to bone marrow stem cells at the two higher doses tested. However, the myelosuppressive effects of mitomycin C were not altered by DDTC administration (300 mg/kg i.v. 3 h after or 30 min before mitomycin C). These results demonstrate that DDTC ameliorates myelotoxicity induced by several, but not all, chemotherapeutic agents and suggest a broad role for DDTC in cancer chemotherapy.
本文报道了二乙基二硫代氨基甲酸盐（DDTC）对C57BL/6J×DBA/2J小鼠中由1,3-双（2-氯乙基）-1-亚硝基脲、阿霉素或丝裂霉素C诱导的骨髓毒性的影响。所有药物均通过静脉注射给药。在给予骨髓毒性药物24小时后，使用骨髓干细胞（脾集落形成单位）和粒细胞/巨噬细胞祖细胞（培养中的粒细胞/巨噬细胞集落形成单位）克隆形成试验评估骨髓毒性。单独给予DDTC对培养中的脾集落形成单位或粒细胞/巨噬细胞集落形成单位没有影响。1,3-双（2-氯乙基）-1-亚硝基脲对两种细胞类型均显示出剂量依赖性毒性，随后用DDTC（在1,3-双（2-氯乙基）-1-亚硝基脲后3小时静脉注射300mg/kg）治疗可减轻这种毒性。在测试的两个较高剂量下，相同给药方案的DDTC减轻了阿霉素对骨髓干细胞的诱导毒性。然而，丝裂霉素C的骨髓抑制作用并未因DDTC给药（在丝裂霉素C后3小时或前30分钟静脉注射300mg/kg）而改变。这些结果表明，DDTC可减轻几种但并非所有化疗药物诱导的骨髓毒性，并提示DDTC在癌症化疗中具有广泛作用。
