Bence J, Somfai-Relle S, Gáti E
Eur J Cancer Clin Oncol. 1986 Jul;22(7):773-80. doi: 10.1016/0277-5379(86)90362-7.
Repeated intraperitoneal treatment of standard P388 mouse leukemia with dianhydrogalactitol (DAG) resulted in the development of a P388/DAG experimental mouse tumor which was resistant to the drug. Resistance was stable without DAG treatment throughout 80 passages. P388/DAG shows cross-resistance to alkylating agents such as nitrogen-mustard, cyclophosphamide and diacetyl-DAG but not to selected antimetabolites and tubulin binders and exhibits reduced sensitivity to nitrosoureas. Resistance to DAG could not be overcome by the administration of maximally tolerated dose of DAG to tumor bearing mice. The resistant tumor is one chromosome short and shows a 13-fold increase of cells possessing a submetacentric marker chromosome.
用双脱水半乳糖醇(DAG)对标准P388小鼠白血病进行反复腹腔内治疗,导致产生了对该药物耐药的P388/DAG实验小鼠肿瘤。在整个80代传代过程中,不进行DAG治疗时,耐药性保持稳定。P388/DAG对烷化剂如氮芥、环磷酰胺和二乙酰-DAG表现出交叉耐药性,但对选定的抗代谢物和微管蛋白结合剂无交叉耐药性,并且对亚硝基脲类药物的敏感性降低。给荷瘤小鼠给予最大耐受剂量的DAG并不能克服对DAG的耐药性。耐药肿瘤缺少一条染色体,并且具有亚中着丝粒标记染色体的细胞增加了13倍。