概括
乙烯基酸盐和乙烯基酸主要修改核酸氧基. 在单链RNA/DNA和双链DNA之间,反应性不同,O2-alkylpyrimidines显示出可变的糖化键.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 化学致癌发生的原因
背景情况:
- 乙酸盐 (ENU) 和乙酸盐 (ENNG) 是已知修改核酸的化剂.
- 了解这些修饰的特定部位和相对反应性对于评估突变性和致癌潜力至关重要.
研究的目的:
- 调查ENU和ENNG对核酸进行改造的首选地点.
- 为了比较单链RNA,单链DNA和双链DNA中的氧气反应模式.
主要方法:
- 核酸 (RNA和DNA) 的化学修饰使用ENU和ENNG.
- 修饰部位的分析,重点是氧原子 (不包括核糖和酸盐).
主要成果:
- 超过80%的ENU和ENNG修饰发生在核酸的氧原子上.
- 在单链RNA中,氧的反应性按照下面的顺序进行:O2 (??) >O2 (??) >Uracil (??) >O6 (??) >O4 (??).
- 在双链DNA中,序列是:O2 (?? 胺) =O6 (?? 氨) >O4 (?? 胺) >O2 (?? 细胞素),而单链DNA的反应性与RNA相似.
- 在O2-基化金胺中,甘氨酸键是不稳定的.
结论:
- 氧原子是核酸中ENU和ENNG化的主要标.
- 对于不同核酸结构 (ssRNA,ssDNA,dsDNA) 中的氧气修饰存在不同的反应模式.
- 在O2-基化金胺中观察到的甘氨酸键的可变性表明了DNA损伤和突变的潜在机制.
更多相关视频
09:33Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
12:15Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
相关概念视频
Oxidations of Aldehydes and Ketones to Carboxylic Acids
Oxidation of aldehydes and ketones results in the formation of carboxylic acids. Aldehydes, bearing hydrogen next to the carbonyl group, are easily oxidized compared to ketones. This is because an aldehydic proton can easily be abstracted during oxidation.
Aldehydes readily undergo oxidation in strong oxidizing agents such as potassium permanganate and chromic acid. The oxidation can also be carried out using mild oxidizing agents such as silver oxide. In fact, aldehydes can be easily oxidized...
Aldehydes readily undergo oxidation in strong oxidizing agents such as potassium permanganate and chromic acid. The oxidation can also be carried out using mild oxidizing agents such as silver oxide. In fact, aldehydes can be easily oxidized...
Toxic Reactions: Overview
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Mutagenicity and Carcinogenicity
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Phase I Reactions: Oxidation of Carbon-Heteroatom and Miscellaneous Systems
Oxidative reactions are pivotal in metabolizing numerous compounds, including pharmaceutical drugs. These reactions often occur in carbon-heteroatom systems, such as carbon-nitrogen, carbon-sulfur, and carbon-oxygen.
In carbon-nitrogen systems, aliphatic and aromatic amines can undergo oxidative reactions. Secondary and tertiary amines, like those found in tricyclic antidepressants, can undergo N-dealkylation, a process that involves the oxidation of the alkyl group. In addition, oxidative...
In carbon-nitrogen systems, aliphatic and aromatic amines can undergo oxidative reactions. Secondary and tertiary amines, like those found in tricyclic antidepressants, can undergo N-dealkylation, a process that involves the oxidation of the alkyl group. In addition, oxidative...
Bioactivation and Tissue Toxicity
Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
