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氧化 DNA 损伤是 4-硝基喹啉 1-氧化物诱导大鼠舌致癌作用的初始步骤。

Oxidative DNA damage is a preliminary step during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

机构信息

Departamento de Patologia, Universidade Federal de Sao Paulo, UNIFESP, Santos, SP, Brazil.

出版信息

J Mol Histol. 2011 Apr;42(2):181-6. doi: 10.1007/s10735-011-9323-9. Epub 2011 Mar 23.

Abstract

The aim of this study was to investigate oxidative DNA damage during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. For this purpose, male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. The alkaline Comet assay modified with lesion-specific enzymes was used to detect single and double strand breaks, labile sites (SBs), and oxidised purines and pyrimidines. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, oxidative DNA damage was detected in the 'normal' oral epithelium. In pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks following carcinogen exposure, respectively, oxidative DNA damage was also increased (P < 0.05) when compared to negative control. In conclusion, our results suggest that oxidative DNA damage is an early event during multistep carcinogenesis assay induced by 4NQO. This kind of approach should be considered to persons with high risk of oral cancer, such as in smokers or alcohol consumers.

摘要

本研究旨在探讨 4-硝基喹啉 1-氧化物(4NQO)诱导大鼠舌癌发生过程中的氧化 DNA 损伤。为此,将雄性 Wistar 大鼠分为三组,每组 10 只,通过饮用水给予 50ppm 的 4NQO 溶液,处理 4、12 和 20 周。10 只动物作为阴性对照。使用经损伤特异性酶修饰的碱性彗星试验来检测单链和双链断裂、不稳定位点(SBs)以及氧化嘌呤和嘧啶。尽管在致癌物暴露的第 4 周,上皮组织未引起组织病理学异常,但在“正常”口腔上皮中已检测到氧化 DNA 损伤。在致癌剂暴露 12 和 20 周后分别诱导的癌前病变和鳞状细胞癌中,与阴性对照组相比,氧化 DNA 损伤也增加(P<0.05)。综上所述,我们的结果表明,氧化 DNA 损伤是 4NQO 诱导的多步骤致癌试验中的早期事件。这种方法应考虑用于具有高口腔癌风险的人群,如吸烟者或饮酒者。

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