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8-oxo-dGTP curbs tumor development via S phase arrest and AIF-mediated apoptosis

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机构： [1]The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China [2]Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, PR China [3]Department of Laboratory Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China [4]Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China [5]Children’s Mercy Research Institute, Kansas City, MO, 64108, USA

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关键词： MTH1 8-oxo-dGTP 8-oxoGTP tumorigenesis tumor inhibition

摘要：

Oxidative stress can attack precursor nucleotides, resulting in nucleic acid damage in cells. It remains unclear how 8-oxo-dGTP and 8-oxoGTP, oxidized forms of dGTP and GTP, respectively, could affect DNA or RNA oxidation levels and tumor development. To address this, we intravenously administered 8-oxo-dGTP and 8-oxoGTP to wild-type and MTH1-knockout mice. 8-oxoGTP administration increased frequency of tumor incidence, which is more prominent in MTH1-knockout mice. However, 8-oxo-dGTP treatment rather reduced tumor development regardless of the mouse genotype. The tumor suppressive effects of 8-oxo-dGTP were further confirmed using xenograft and C57/6J-ApcMin/Nju mouse models. Mechanistically, 8-oxo-dGTP increased the 8-oxo-dG contents in DNA and DNA strand breakage, induced cell cycle arrest in S phase and apoptosis mediated by AIF, eventually leading to reduced tumor incidence. These results suggest distinct roles of 8-oxo-dGTP and 8-oxoGTP in tumor development.Copyright © 2023. Published by Elsevier Inc.

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出版当年[2023]版：

大类 | 2 区

生物学

小类 | 2 区生化与分子生物学 2 区内分泌学与代谢

最新[2023]版：

大类 | 2 区

生物学

小类 | 2 区生化与分子生物学 2 区内分泌学与代谢

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第一作者机构： [1]The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China

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通讯机构： [1]The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China [*1]The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission Institute of Geriatric Medicine, Chinese Academy of Medical Sciences. No. 1 Dahua Road, Beijing, 100730, China.

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8-oxo-dGTP curbs tumor development via S phase arrest and AIF-mediated apoptosis

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