Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts:: involvement of two excision repair mechanisms in vitro
Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts:: involvement of two excision repair mechanisms in vitro
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DOI：
10.1093/carcin/19.7.1239
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发表时间：
1998-07-01
期刊：
影响因子：
4.7
通讯作者：
Wang, ZG
中科院分区：
文献类型：
--
作者：
Braithwaite, E;Wu, XH;Wang, ZG
多环芳烃（PAH）是重要的环境污染物，是人类癌症的重要危险因素。 PAHs 最终致癌物形成的 DNA 加合物具有潜在的毒性、致突变性和致癌性。 DNA 修复代表了针对这些基因毒性损伤的重要防御系统，使用人类无细胞系统，我们检查了由几种 PAH 二氢二醇环氧化物诱导的 DNA 损伤的修复，包括抗（+/-）-苯并[a]芘-反式-7,8-二氢二醇-9,10-环氧化物、抗-（+/-）-苯并[a]蒽-反式-3,4-二氢二醇-1,2-环氧化物、抗(+/-)-苯并[a]蒽-反式-8,9-二氢二醇-10,11-环氧化物、抗-(+/-)-苯并[b]荧蒽-反式-9,10-二氢二醇-11,12-环氧化物和反-(+/-)-屈-反式-1,2-二氢二醇-3,4-环氧化物。检测到这五种 PAH 代谢物诱导的 DNA 损伤的有效修复，观察到两种不同的切除修复机制。主要的修复机制是核苷酸切除修复（NER），另一种机制独立于NER，与受损DNA中脱嘌呤/脱嘧啶位点的存在相关，因此可能反映了碱基切除修复（BER）。然而，BER 在体外对不同 PAH 损伤的贡献有所不同，这些结果表明 BER 也可能在某些 PAM 诱导的 DNA 损伤的修复中发挥重要作用。
Polycyclic aromatic hydrocarbons (PAHs) are significant environmental pollutants representing an important risk factor in human cancers. DNA adducts formed by the ultimate carcinogens of PAHs are potentially toxic, mutagenic and carcinogenic. DNA repair represents an important defense system against these genotoxic insults, Using a human cell-free system we have examined repair of DNA lesions induced by several PAH dihydrodiol epoxides, including anti-(+/-)-benzo[a]pyrene-trans-7,8-dihydrodiol- 9,10-epoxide, anti-(+/-)-benz[a]anthracene-trans-3,4-dihydro- diol-1,2-epoxide, anti-(+/-)-benz[a]anthracene-trans-8,9-dihydro diol-10,11-epoxide, anti-(+/-)-benzo[b]fluoranthene-trans-9,10-dihydrodiol-11,12-epoxide and anti-(+/-)-chrysene-trans-1,2-dihydrodiol-3,4-epoxide. Effective repair of DNA damage induced by these five PAH metabolites was detected, Two distinct mechanisms of excision repair were observed. The major repair mechanism is nucleotide excision repair (NER), The other mechanism is independent of NER and correlated with the presence of apurinic/apyrimidinic sites in the damaged DNA, thus presumably reflecting base excision repair (BER). However, the contribution of BER to different PAH lesions varied in vitro, These results suggest the possibility that BER may also play an important role in repair of certain PAM-induced DNA lesions.