Anderson T, McMenamin M G, Schein P S
Cancer Res. 1975 Mar;35(3):761-5.
Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, is a newly synthesized, water-soluble nitrosourea antitumor agent that is active against L1210 leukemia in mice. A 701% and a 401% increase in life-span were attained with a dose that was lethal to 10% of the animals (15 to 20 mg/kg, i.p.) in mice treated on Day 2 or Day 6 of L1210 tumor growth, respectivley. Sixity % of Day 2-treated mice and 30% of Day 6-treated mice survived for 90 days. At the maximally effective dose against L1210, chlorozotocin produced no significant depression in normal bone marrow DNA synthesis nor in peripheral neutrophil count, in contrast to a sustained greater than 90% inhibition in L1210 ascites cell DNA synthesis. If the antitumor activity and reduced bone marrow toxicity of chlorozotocin are confirmed in man the use of this compound would facilitate treatment of patients with neoplastic disease who have preexisting abnormal bone marrow function or would allow for the more effective use of a nitrosourea agent in combination with anticancer agents possessing more potent myelosuppressive properties.
氯脲霉素，即2-(3-(2-氯乙基)-3-亚硝基脲基)-D-吡喃葡萄糖，是一种新合成的水溶性亚硝基脲类抗肿瘤药物，对小鼠L1210白血病具有活性。在L1210肿瘤生长的第2天或第6天分别用对10%的动物（15至20毫克/千克，腹腔注射）致死的剂量处理小鼠，可使生存期分别延长701%和401%。第2天处理的小鼠中有60%以及第6天处理的小鼠中有30%存活了90天。与对L1210腹水细胞DNA合成持续大于90%的抑制相反，在对L1210的最大有效剂量下，氯脲霉素对正常骨髓DNA合成和外周中性粒细胞计数均无显著抑制作用。如果氯脲霉素的抗肿瘤活性和降低的骨髓毒性在人体中得到证实，那么该化合物的使用将有助于治疗已有骨髓功能异常的肿瘤患者，或者能够更有效地将亚硝基脲类药物与具有更强骨髓抑制特性的抗癌药物联合使用。
