Bodell W J
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143-0520.
Mutat Res. 1990 Nov-Dec;233(1-2):203-10. doi: 10.1016/0027-5107(90)90163-x.
The induction of sister-chromatid exchanges (SCEs) and cytotoxicity in 9L cells treated with monofunctional and bifunctional alkylating agents has been investigated. Three classes of monofunctional and bifunctional agents were studied: nitrosoureas, mustards and epoxides. Independent of class the bifunctional agents were 55-630-fold more effective at inducing SCEs and 300-2400-fold more effective at inducing cellular cytotoxicity than the corresponding monofunctional agents. Comparing the induction of SCEs and cytotoxicity by these agents showed that these two cellular responses to DNA damage are highly correlated. The extent of DNA alkylation in cells treated with 1-ethyl-1-nitrosourea (ENU) or 1-(2-chloro-ethyl)-1-nitrosourea (CNU) was similar indicating that the increased effectiveness of CNU to induce SCEs and cytotoxicity was not due to increased DNA alkylation. Molecular dosimetry calculations indicate that for CNU and ENU treatment of 9L cells there are 116 and 8500 alkylations per SCE induced and 2.6 x 10(4) and 4.6 x 10(6) alkylations at the dose required to reduce survival of 9L cells by 90%. Comparison of the DNA alkylation products produced by CNU and ENU treatment of 9L cells suggests that the formation of the intrastrand crosslink N7-bis(guanyl)ethane and the interstrand crosslink 1-(3-deoxycytidyl)-2-(1-deoxyguanosinyl)ethane by CNU is responsible for the increased effectiveness of CNU treatment at both induction of SCEs and cytotoxicity.
对用单功能和双功能烷化剂处理的9L细胞中姐妹染色单体交换（SCE）的诱导及细胞毒性进行了研究。研究了三类单功能和双功能试剂：亚硝基脲、芥子气和环氧化物。与相应的单功能试剂相比，双功能试剂在诱导SCE方面的效力高55 - 630倍，在诱导细胞毒性方面的效力高300 - 2400倍，且与类别无关。比较这些试剂诱导SCE和细胞毒性的情况表明，这两种细胞对DNA损伤的反应高度相关。用1 - 乙基 - 1 - 亚硝基脲（ENU）或1 - （2 - 氯乙基） - 1 - 亚硝基脲（CNU）处理的细胞中DNA烷基化程度相似，这表明CNU诱导SCE和细胞毒性的效力增加并非由于DNA烷基化增加。分子剂量学计算表明，对于9L细胞用CNU和ENU处理，每诱导一个SCE分别有116和8500次烷基化，在使9L细胞存活率降低90%所需的剂量下分别有2.6×10⁴和4.6×10⁶次烷基化。对9L细胞用CNU和ENU处理产生的DNA烷基化产物的比较表明，CNU形成链内交联N7 - 双（鸟嘌呤基）乙烷和链间交联1 - （3 - 脱氧胞苷基） - 2 - （1 - 脱氧鸟苷基）乙烷是CNU在诱导SCE和细胞毒性方面效力增加的原因。
