Dean S W, Tew K D, Clark A E, Schein P S
Br J Cancer. 1985 Sep;52(3):377-82. doi: 10.1038/bjc.1985.204.
Previous studies have suggested that 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl) -3-nitrosoureahydrochloride (ACNU) and 1,(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) bind specifically to the nucleosomal DNA of murine bone marrow and L1210 leukaemia cells whereas the glucose nitrosoureas, 2-(3-(2-chloroethyl)-3-nitrosoureido)-2-deoxy-D-glucopyranose, (chlorozotocin, CLZ) and 1-(2-chloroethyl)-3-(-D-glucopyranosyl)-1-nitrosourea (GANU), bind preferentially to the linker DNA of bone marrow but not tumour cell chromatin. In order to provide an explanation for this differential, the DNA repeat and linker lengths in murine bone marrow and L1210 leukaemia cells were measured using electrophoresis of micrococcal nuclease-digested DNA. The linker length of bone marrow chromatin was approximately 22% longer than that in L1210 leukaemia cells from mouse ascites. The linker length of L1210 cells maintained in suspension culture was 27% less than in those from ascites fluid. The tissue-specific toxicity of sugar nitrosoureas and the differential binding of these drugs to chromatin does not appear to correlate quantitatively with differences in DNA linker length.
先前的研究表明，1-(4-氨基-2-甲基嘧啶-5-基)-甲基-3-(2-氯乙基)-3-亚硝基脲盐酸盐（ACNU）和1-(2-氯乙基)-3-环己基-1-亚硝基脲（CCNU）能特异性结合小鼠骨髓和L1210白血病细胞的核小体DNA，而葡萄糖亚硝基脲，2-(3-(2-氯乙基)-3-亚硝基脲基)-2-脱氧-D-吡喃葡萄糖（氯脲霉素，CLZ）和1-(2-氯乙基)-3-(β-D-吡喃葡萄糖基)-1-亚硝基脲（GANU），则优先结合骨髓的连接DNA，而非肿瘤细胞染色质。为了解释这种差异，利用微球菌核酸酶消化的DNA进行电泳，测量了小鼠骨髓和L1210白血病细胞中的DNA重复序列和连接长度。骨髓染色质的连接长度比来自小鼠腹水的L1210白血病细胞中的连接长度长约22%。悬浮培养的L1210细胞的连接长度比腹水中的细胞短27%。糖亚硝基脲的组织特异性毒性以及这些药物与染色质的差异结合似乎与DNA连接长度的差异在数量上并无关联。
