2'-脱氧助间型霉素、9-β-D-阿拉伯呋喃糖基腺嘌呤5'-磷酸酯和1-β-D-阿拉伯呋喃糖基胞嘧啶三联联合疗法对脑内白血病1210的影响

Effects of 2'-deoxycoformycin, 9-beta-D-arabinofuranosyladenine 5'-phosphate, and 1-beta-D-arabinofuranosylcytosine triple combination therapy on intracerebral leukemia 1210.

作者信息

Caron N, Lee S H, Kimball A P

出版信息

Cancer Res. 1977 Sep;37(9):3274-9.

Abstract

The triple combination of 2'-deoxycoformycin (2'-dCF), 9-beta-D-arabinofuranosyladenine 5'-phosphate, and 9-beta-D-arabinofuranosylcytosine was found to be very effective in the therapy of C57BL X DBA/2 F1 mice with intracerebral L1210. At the dosages and dosage scheduling used, the double combination of 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate gave minimal but significant increases in life-span. When 9-beta-D-arabinofuranosylcytosine was given at suboptimal dosage to mice with intracerebral L1210, the host toxicity caused by 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate in combination was decreased by a factor of 2, allowing a more prolonged therapy. "Cures" were obtained with the triple combination at dosages of 9-beta-D-arabinofuranosylcytosine that did not "cure". The supernatant adenosine deaminase from C57BL X DBA/2 F1 mouse brains was purified and the Ki for 2'-dCF using 9-beta-D-arabinofuranosyladenine as substrate was determined to be not more than 2 X 10(-11) M.

摘要

发现2'-脱氧助间型霉素（2'-dCF）、9-β-D-阿拉伯呋喃糖基腺嘌呤5'-磷酸和9-β-D-阿拉伯呋喃糖基胞嘧啶的三联组合对患有脑内L1210肿瘤的C57BL×DBA/2 F1小鼠的治疗非常有效。在所使用的剂量和给药方案下，2'-dCF与9-β-D-阿拉伯呋喃糖基腺嘌呤5'-磷酸的双联组合使寿命有最小但显著的增加。当以次优剂量给患有脑内L1210肿瘤的小鼠施用9-β-D-阿拉伯呋喃糖基胞嘧啶时，2'-dCF与9-β-D-阿拉伯呋喃糖基腺嘌呤5'-磷酸联合引起的宿主毒性降低了2倍，从而允许进行更长时间的治疗。用三联组合在9-β-D-阿拉伯呋喃糖基胞嘧啶的剂量下获得了“治愈”效果，而该剂量单独使用时不能“治愈”。对C57BL×DBA/2 F1小鼠脑的上清液腺苷脱氨酶进行了纯化，并确定以9-β-D-阿拉伯呋喃糖基腺嘌呤为底物时2'-dCF的抑制常数（Ki）不超过2×10^(-11) M。