Bodell W J, Aida T, Rasmussen J
Mutat Res. 1985 Mar;149(1):95-100. doi: 10.1016/0027-5107(85)90013-2.
We have investigated the induction of sister-chromatid exchanges (SCEs) in 9L rat brain tumor cells treated with the alkylating agent 1-ethyl-1-nitrosourea (ENU) and 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1-nitrosourea (ACNU), an agent that both alkylates and crosslinks DNA. Induction of SCEs by ACNU was found to be 143-fold greater than for ENU. However, on an equimolar basis, the alkylation of DNA by 14C-ACNU was approximately 3.2-fold higher than for 14C-ENU. After correction for this difference was made, the induction of SCEs by ACNU was calculated to be 45-fold greater than for ENU. While DNA alkylation products formed by ACNU and ENU are similar, the chloroethyl alkylation product(s) of ACNU can form DNA-interstrand crosslinks; the ethyl alkylation product(s) of ENU cannot. Based on these findings, we propose that the increased induction of SCEs caused by ACNU is a result of the formation of DNA interstrand crosslinks.
我们研究了用烷化剂1-乙基-1-亚硝基脲（ENU）和3-(4-氨基-2-甲基-5-嘧啶基)甲基-1-(2-氯乙基)-1-亚硝基脲（ACNU，一种既能使DNA烷基化又能使其交联的试剂）处理的9L大鼠脑肿瘤细胞中姐妹染色单体交换（SCE）的诱导情况。发现ACNU诱导SCE的能力比ENU高143倍。然而，在等摩尔基础上，14C-ACNU对DNA的烷基化作用比14C-ENU高约3.2倍。校正这一差异后，计算得出ACNU诱导SCE的能力比ENU高45倍。虽然ACNU和ENU形成的DNA烷基化产物相似，但ACNU的氯乙基烷基化产物能形成DNA链间交联，而ENU的乙基烷基化产物则不能。基于这些发现，我们提出ACNU导致SCE诱导增加是DNA链间交联形成的结果。
