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Effects of Black Raspberry Extract and Berry Compounds on Repair of DNA Damage and Mutagenesis Induced by Chemical and Physical Agents in Human Oral Leukoplakia and Rat Oral Fibroblasts
Chemical Research in Toxicology ( IF 4.1 ) Pub Date : 2017-11-15 00:00:00 , DOI: 10.1021/acs.chemrestox.7b00242
Joseph B. Guttenplan 1, 2 , Kun-Ming Chen , Yuan-Wan Sun , Braulio Lajara 1 , Nora A. E. Shalaby 1 , Wieslawa Kosinska 1 , Gabrielle Benitez , Krishne Gowda , Shantu Amin , Gary Stoner 3 , Karam El-Bayoumy
Affiliation  

Black raspberries (BRB) have been shown to inhibit carcinogenesis in a number of systems, with most studies focusing on progression. Previously we reported that an anthocyanin-enriched black raspberry extract (BE) enhanced repair of dibenzo-[a,l]-pyrene dihydrodiol (DBP-diol)-induced DNA adducts and inhibited DBP-diol and DBP-diolepoxide (DBPDE)-induced mutagenesis in a lacI rat oral fibroblast cell line, suggesting a role for BRB in the inhibition of initiation of carcinogenesis. Here we extend this work to protection by BE against DNA adduct formation induced by dibenzo-[a,l]-pyrene (DBP) in a human oral leukoplakia cell line (MSK) and to a second carcinogen, UV light. Treatment of MSK cells with DBP and DBPDE led to a dose-dependent increase in DBP-DNA adducts. Treatment of MSK cells with BE after addition of DBP reduced levels of adducts relative to cells treated with DBP alone, and treatment of rat oral fibroblasts with BE after addition of DBPDE inhibited mutagenesis. These observations showed that BE affected repair of DNA adducts and not metabolism of DBP. As a proof of principle we also tested aglycones of two anthocyanins commonly found in berries, delphinidin chloride and pelargonidin chloride. Delphinidin chloride reduced DBP-DNA adduct levels in MSK cells, while PGA did not. These results suggested that certain anthocyanins can enhance repair of bulky DNA adducts. As DBP and its metabolites induced formation of bulky DNA adducts, we investigated the effects of BE on genotoxic effects of a second carcinogen that induces bulky DNA damage, UV light. UV irradiation produced a dose-dependent increase in cyclobutanepyrimidine dimer levels in MSK cells, and post-UV treatment with BE resulted in lower cyclobutanepyrimidine dimer levels. Post-UV treatment of the rat lacI cells with BE reduced UV-induced mutagenesis. Taken together, the results demonstrate that BE extract reduces bulky DNA damage and mutagenesis and support a role for BRB in the inhibition of initiation of carcinogenesis.

中文翻译:

黑莓提取物和浆果化合物对人口腔白斑和大鼠口腔成纤维细胞化学和物理试剂诱导的DNA损伤和诱变的修复作用

黑莓(BRB)已显示在许多系统中抑制癌变,大多数研究集中在进展上。以前我们报道过,富含花青素的黑树莓提取物(BE)增强了对二苯并[ a,l ] -py二氢二醇(DBP-diol)诱导的DNA加合物的修复,并抑制了DBP-二醇和DBP-二醇环氧(DBPDE)诱导的lacI大鼠口腔成纤维细胞系中发生诱变,表明BRB在抑制致癌作用的启动中发挥了作用。在这里,我们将这项工作扩展到BE的保护,以防止由二苯并[[ a,l]人口腔白斑细胞系(MSK)中的] -py(DBP)以及第二种致癌物紫外线。用DBP和DBPDE处理MSK细胞导致DBP-DNA加合物的剂量依赖性增加。与仅用DBP处理的细胞相比,添加DBP后用BE处理MSK细胞可降低加合物的水平,而在添加DBPDE后用BE处理大鼠口腔成纤维细胞可抑制诱变。这些观察结果表明,BE影响DNA加合物的修复,而不影响DBP的代谢。作为原理上的证明,我们还测试了浆果中常见的两种花色苷的糖苷配基,分别是氯化翠雀碱和氯化壬二酚。氯化Delphinidin降低了MSK细胞中DBP-DNA加合物的水平,而PGA则没有。这些结果表明某些花色苷可以增强大体积DNA加合物的修复。由于DBP及其代谢物诱导了大体积DNA加合物的形成,我们研究了BE对第二种引起大体积DNA损伤的致癌物(紫外线)的遗传毒性作用。紫外线辐射在MSK细胞中产生剂量依赖性的环丁烷嘧啶二聚体水平增加,而用BE进行紫外线后处理则导致较低的环丁烷嘧啶二聚体水平。紫外线后对大鼠的治疗具有BE的lacI细胞减少了UV诱导的诱变。两者合计,结果表明BE提取物减少了庞大的DNA损伤和诱变作用,并支持BRB在抑制致癌作用中的作用。
更新日期:2017-11-16
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