Involvement of DNA polymerase β overexpression in the malignant transformation induced by benzo[a]pyrene.
Involvement of DNA polymerase β overexpression in the malignant transformation induced by benzo[a]pyrene.
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DOI：
10.1016/j.tox.2013.04.017
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发表时间：
2013-07-05
期刊：
影响因子：
4.5
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhao W;Wu M;Lai Y;Deng W;Liu Y;Zhang Z
探讨DNA聚合酶β (pol β)过表达与苯并[a]芘（BaP）致癌的关系。首先，用不同浓度的BaP处理表达野生型DNA聚合酶β （pol β细胞）和高水平pol β （pol β oe细胞）的小鼠胚胎成纤维细胞，观察BaP在不同pol β表达水平下诱导的遗传不稳定性。其次，采用软琼脂集落形成法和转化焦点法测定低浓度（20 μM） BaP对pol β细胞的恶性转化。再次，采用逆转录聚合酶链反应（RT-PCR）和western blot检测bap转化的pol β细胞（称为pol β- t细胞）mRNA和蛋白水平，并采用HPRT基因突变和RAPD检测这些细胞的遗传不稳定性。低浓度BaP作用6个月后，Pol β细胞成功转化为恶性Pol β- t细胞。Pol β- t细胞的Pol β基因表达水平、HPRT基因突变频率和RAPD产物多态性与Pol β- e细胞相当。Pol β过表达及其相关的遗传不稳定性可能在BaP致癌过程中起关键作用。
To explore the relationship between DNA polymerase β (pol β) overexpression and benzo[a]pyrene (BaP) carcinogenesis. Firstly, mouse embryonic fibroblasts that express wild-type level of DNA polymerase β (pol β cell) and high level of pol β (pol β oe cell) were treated by various concentrations of BaP to determine genetic instability induced by BaP under differential expression levels of pol β. Secondly, malignant transformation of pol β cells by low concentration of BaP (20 μM) was determined by soft agar colony formation assay and transformation focus assay. Thirdly, the mRNA and protein levels of BaP-transformed pol β cells (named pol β-T cells) was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, and the genetic instability of these cells were examined by HPRT gene mutation assay and random amplified polymorphic DNA (RAPD) assay. Pol β cells were successfully transformed into malignant pol β-T cells by an exposure to low concentration of BaP for 6 months. Pol β-T cells exhibited increased levels of pol β gene expression, HPRT gene mutation frequency and polymorphisms of RAPD products that were comparable to those of pol β oe cells. Pol β overexpression and its-associated genetic instability may play a key role in BaP carcinogenesis.
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