Expression of base excision repair enzymes in rat and mouse liver is induced by peroxisome proliferators and is dependent upon carcinogenic potency.
Expression of base excision repair enzymes in rat and mouse liver is induced by peroxisome proliferators and is dependent upon carcinogenic potency.
复制标题
大鼠和小鼠肝脏中碱基切除修复酶的表达是由过氧化物酶体增殖剂诱导的，并且取决于致癌效力。
DOI：
10.1093/carcin/21.12.2141
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发表时间：
2000
期刊：
影响因子：
4.7
通讯作者：
Swenberg,JA
中科院分区：
文献类型：
--
作者：
Rusyn,I;Denissenko,MF;Wong,VA;Butterworth,BE;Cunningham,ML;Upton,PB;Thurman,RG;Swenberg,JA
细胞复制的升高和持续以及细胞凋亡的减少被认为是过氧化物酶体增殖剂促进肝肿瘤的主要机制。相比之下，氧化应激和 DNA 损伤在致癌机制中的作用尚不清楚。鉴于过氧化物酶体增殖剂可能诱导DNA损伤，DNA修复机制可能是这些化合物作用机制中需要考虑的重要因素。在此，检查了过氧化物酶体增殖剂诱导碱基切除修复酶表达的能力。 WY-14,643 是一种强效致癌物，能够以剂量和时间依赖性方式增加多种碱基切除 DNA 修复酶的表达。重要的是，不修复DNA氧化损伤的酶的表达没有改变。此外，与 WY-14,643 相比，过氧化物酶体增殖剂组中效力较低的成员对 DNA 修复酶表达的影响要弱得多或没有影响。总的来说，这些数据表明DNA碱基切除修复可能是过氧化物酶体增殖物诱导的癌发生的一个重要因素，并且DNA修复的诱导可能提供进一步的证据支持过氧化物酶体增殖物氧化DNA损伤的作用。
Elevated and sustained cell replication, together with a decrease in apoptosis, is considered to be the main mechanism of hepatic tumor promotion due to peroxisome proliferators. In contrast, the role of oxidative stress and DNA damage in the carcinogenic mechanism is less well understood. In view of possible induction of DNA damage by peroxisome proliferators, DNA repair mechanisms may be an important factor to consider in the mechanism of action of these compounds. Here, the ability of peroxisome proliferators to induce expression of base excision repair enzymes was examined. WY-14,643, a potent carcinogen, increased expression of several base excision DNA repair enzymes in a dose- and time-dependent manner. Importantly, expression of enzymes that do not repair oxidative DNA damage was not changed. Moreover, less potent members of the peroxisome proliferator group had much weaker or no effects on expression of DNA repair enzymes when compared with WY-14,643. Collectively, these data suggest that DNA base excision repair may be an important factor in peroxisome proliferator-induced carcinogenesis and that induction of DNA repair might provide further evidence supporting a role of oxidative DNA damage by peroxisome proliferators.