Lawson T, Gwilt P R
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Cancer Lett. 1993 Jun 15;70(1-2):119-22. doi: 10.1016/0304-3835(93)90083-l.
The ability of N-ethyl-N-nitrosourea (ENU) to produce single strand breaks (SSB) and N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) to produce SSB and DNA-DNA interstrand cross-links was measured in L1210 cells that had been pretreated with clofibrate (CLO). When ENU was used the SSB frequency rose from 12.4 +/- 1.6/10(6) bases in control cells to 17.3 +/- 1.5/10(6) bases in CLO-treated cells and from 2.8 +/- 0.1/10(6) bases in control cells to 5.5 +/- 0.4/10(6) in CLO-treated cells when BCNU was the damaging agent. Similarly the cross-linking frequency rose from 3.5 +/- 0.1/10(6) bases in control cells to 12.1 +/- 0.5/10(6) bases in CLO-treated cells when BCNU was the cross-linking agent. CLO treatment increased the production of superoxide anion four-fold over the controls and it increased the cytotoxicity of BCNU. Forty-two percent of the control+BCNU cells survived after 24 h whereas only 24% of the CLO+BCNU cells survived. The stimulation of the diffuse condition known as oxidative stress increased the interaction of nitrosoureas with DNA and resulted in increased biological responses, e.g. cytotoxicity.
在已用氯贝丁酯（CLO）预处理的L1210细胞中，测定了N-乙基-N-亚硝基脲（ENU）产生单链断裂（SSB）的能力以及N，N'-双（2-氯乙基）-N-亚硝基脲（BCNU）产生SSB和DNA-DNA链间交联的能力。当使用ENU时，单链断裂频率从对照细胞中的12.4±1.6/10⁶个碱基增加到CLO处理细胞中的17.3±1.5/10⁶个碱基；当BCNU作为损伤剂时，从对照细胞中的2.8±0.1/10⁶个碱基增加到CLO处理细胞中的5.5±0.4/10⁶个碱基。同样，当BCNU作为交联剂时，交联频率从对照细胞中的3.5±0.1/10⁶个碱基增加到CLO处理细胞中的12.1±0.5/10⁶个碱基。CLO处理使超氧阴离子的产生量比对照增加了四倍，并且增加了BCNU的细胞毒性。对照 + BCNU组细胞在24小时后有42%存活，而CLO + BCNU组细胞只有24%存活。对称为氧化应激的弥漫状态的刺激增加了亚硝基脲与DNA的相互作用，并导致生物反应增加，例如细胞毒性。
