8-Hydroxy-2'-deoxyguanosine is a key biomarker of oxidative stress-induced DNA damage, used to assess the risk of various cancers and degenerative diseases[1]. 8-Hydroxy-2'-deoxyguanosine is produced when reactive oxygen species (such as hydroxyl radicals and peroxynitrite) attack the guanine base in DNA molecules, and can lead to G:C→T:A transversions during DNA replication, thereby playing an important role in gene mutation, carcinogenesis, and cellular senescence[2]. 8-Hydroxy-2'-deoxyguanosine serves as a biomarker for evaluating the extent of DNA damage in humans exposed to carcinogens such as tobacco smoke, asbestos fibers, heavy metals, and polycyclic aromatic hydrocarbons[3]. The concentration of 8-Hydroxy-2'-deoxyguanosine in the urine of cancer patients is significantly higher than in healthy adults, showing a positive correlation with malignant tumors, thus 8-Hydroxy-2'-deoxyguanosine can be used as a potential auxiliary indicator for tumor diagnosis[4].
In vitro, pretreatment of fully differentiated 3T3-L1 adipocytes with 8-Hydroxy-2'-deoxyguanosine (100μg/mL) for 1 hour, followed by stimulation with TNFα (10ng/mL) for 24 hours, significantly restored insulin-induced Akt phosphorylation levels and suppressed TNFα-induced JNK phosphorylation activation. When 3T3-L1 preadipocytes were treated with 8-Hydroxy-2'-deoxyguanosine (100μg/mL) every other day for 6 days during the differentiation induction phase, 8-Hydroxy-2'-deoxyguanosine significantly inhibited the mRNA expression of aP2, C/EBPα, and PPARγ, and reduced the number and size of mature adipocytes[5].
In vivo, 8-Hydroxy-2'-deoxyguanosine (30mg/kg/day) was administered orally to ApoE knockout mice that had undergone partial carotid artery ligation, for 2 weeks. 8-Hydroxy-2'-deoxyguanosine significantly inhibited high-fat diet-induced atherosclerotic plaque formation and reduced vascular lumen obstruction[6]. In Balb/c nude mice carrying KG-1 human acute myeloid leukemia cell-derived sarcomas, daily intraperitoneal injection of 8-Hydroxy-2'-deoxyguanosine (3.3-330mg/kg/day) for 14 days significantly inhibited KG-1 tumor growth in a dose-dependent manner, as evidenced by reduced tumor volume and weight[7].
References:
[1] AbuArrah M, Yuli Setianto B, Faisal A, et al. 8-Hydroxy-2-Deoxyguanosine as Oxidative DNA Damage Biomarker of Medical Ionizing Radiation: A Scoping Review. J Biomed Phys Eng. 2021 Jun 1;11(3):389-402.
[2] Di Minno A, Turnu L, Porro B, et al. 8-Hydroxy-2-deoxyguanosine levels and heart failure: A systematic review and meta-analysis of the literature. Nutr Metab Cardiovasc Dis. 2017 Mar;27(3):201-208.
[3] Kroese LJ, Scheffer PG. 8-hydroxy-2'-deoxyguanosine and cardiovascular disease: a systematic review. Curr Atheroscler Rep. 2014 Nov;16(11):452.
[4] Alarcón-Sánchez MA, Escoto-Vasquez LS, Heboyan A. Salivary 8-hydroxy-2'-deoxyguanosine levels in patients with oral cancer: a systematic review and meta-analysis. BMC Cancer. 2024 Aug 6;24(1):960.
[5] Huh JY, Jung I, Piao L, et al. 8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance and adipocyte dysfunction in mice. Biochem Biophys Res Commun. 2017 Sep 30;491(4):890-896.
[6] Huh JY, Son DJ, Lee Y, et al. 8-Hydroxy-2-deoxyguanosine prevents plaque formation and inhibits vascular smooth muscle cell activation through Rac1 inactivation. Free Radic Biol Med. 2012 Jul 1;53(1):109-21.
[7] Choi S, Choi HH, Choi JH, et al. Inhibitory effect of 8-oxo-7,8-dihydro-2'-deoxyguanosine on the growth of KG-1 myelosarcoma in Balb/c nude mice. Leuk Res. 2006 Nov;30(11):1425-36.
8-Hydroxy-2'-deoxyguanosine是氧化应激诱导的DNA损伤的关键生物标志物，用于评估多种癌症和退行性疾病的风险[1]。8-Hydroxy-2'-deoxyguanosine由活性氧（如羟基自由基和过氧亚硝酸盐）攻击DNA分子中的鸟嘌呤碱基产生，在DNA复制过程中可导致G:C→T:A的颠换，从而在基因突变、癌变和细胞衰老过程中起重要作用[2]。8-Hydroxy-2'-deoxyguanosine作为评估人类暴露于烟草烟雾、石棉纤维、重金属和多环芳烃等致癌物后DNA损伤程度的生物标志物[3]。癌症患者尿液中8-Hydroxy-2'-deoxyguanosine的浓度显著高于健康成年人，与恶性肿瘤存在正相关，因此可作为肿瘤诊断的潜在辅助指标[4]。
在体外，8-Hydroxy-2'-deoxyguanosine (100μg/mL) 预处理完全分化的3T3-L1脂肪细胞1小时，随后以TNFα (10ng/mL) 刺激24小时，显著恢复胰岛素诱导的Akt磷酸化水平，并抑制TNFα诱导的JNK磷酸化激活，在诱导分化阶段，8-Hydroxy-2'-deoxyguanosine (100μg/mL) 隔日处理3T3-L1前脂肪细胞6天，显著抑制aP2、C/EBPα和PPARγ的mRNA表达，并减少成熟脂肪细胞的数量和体积[5]。
在体内，8-Hydroxy-2'-deoxyguanosine (30mg/kg/day) 通过口服给药，用于处理部分颈动脉结扎的ApoE基因敲除小鼠，持续2周。8-Hydroxy-2'-deoxyguanosine显著抑制了高脂饮食诱导的动脉粥样硬化斑块形成，减少了血管腔的阻塞[6]。8-Hydroxy-2'-deoxyguanosine (3.3-330mg/kg/day) 通过每日腹腔注射给药，持续14天，用于处理携带人急性骨髓性白血病细胞（KG-1）髓系肉瘤的Balb/c裸鼠。8-Hydroxy-2'-deoxyguanosine以剂量依赖方式显著抑制了KG-1肿瘤的生长，表现为肿瘤体积和重量的减少[7]。