Sales Ana H, Kolbanovskiy Marina, Geacintov Nicholas E, Chen Kun-Ming, Sun Yuan-Wan, El-Bayoumy Karam
Department of Chemistry, New York University, New York, NY 10003, USA.
Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
Antioxidants (Basel). 2022 Oct 26;11(11):2110. doi: 10.3390/antiox11112110.
As demonstrated by us earlier and by other researchers, a diet containing freeze-dried black raspberries (BRB) inhibits DNA damage and carcinogenesis in animal models. We tested the hypothesis that the inhibition of DNA damage by BRB is due, in part, to the enhancement of DNA repair capacity evaluated in the human HeLa cell extract system, an established in vitro system for the assessment of cellular DNA repair activity. The pre-treatment of intact HeLa cells with BRB extracts (BRBE) enhances the nucleotide excision repair (NER) of a bulky deoxyguanosine adduct derived from the polycyclic aromatic carcinogen benzo[a]pyrene (BP-dG) by ~24%. The NER activity of an oxidatively-derived non-bulky DNA lesion, guanidinohydantoin (Gh), is also enhanced by ~24%, while its base excision repair activity is enhanced by only ~6%. Western Blot experiments indicate that the expression of selected, NER factors is also increased by BRBE treatment by ~73% (XPA), ~55% (XPB), while its effects on XPD was modest (<14%). These results demonstrate that BRBE significantly enhances the NER yields of a bulky and a non-bulky DNA lesion, and that this effect is correlated with an enhancement of expression of the critically important NER factor XPA and the helicase XPB, but not the helicase XPD.
正如我们之前以及其他研究人员所证明的,含有冻干黑莓(BRB)的饮食可抑制动物模型中的DNA损伤和致癌作用。我们检验了这样一个假设,即BRB对DNA损伤的抑制作用部分归因于在人类HeLa细胞提取物系统中评估的DNA修复能力的增强,该系统是用于评估细胞DNA修复活性的成熟体外系统。用BRB提取物(BRBE)对完整的HeLa细胞进行预处理,可使源自多环芳烃致癌物苯并[a]芘(BP-dG)的大体积脱氧鸟苷加合物的核苷酸切除修复(NER)提高约24%。氧化衍生的非大体积DNA损伤胍基乙内酰脲(Gh)的NER活性也提高了约24%,而其碱基切除修复活性仅提高了约6%。蛋白质免疫印迹实验表明,BRBE处理还使所选NER因子的表达增加了约73%(XPA)、约55%(XPB),而其对XPD的影响较小(<14%)。这些结果表明,BRBE显著提高了大体积和非大体积DNA损伤的NER产量,并且这种作用与关键NER因子XPA和解旋酶XPB表达的增强相关,但与解旋酶XPD无关。