紫外线诱导的DNA损伤和人类黑色素细胞的突变:与黑色素瘤突变的相关性
Seung-Gi Jin1, Jennifer Johnson1, Paul Y Kim1,2
1Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, United States.
Nucleic acids research
|September 18, 2025
概括
紫外线A (UVA) 辐射会在黑色素细胞中引起DNA损伤,但其突变效应有限. 来自UVA的氧化DNA病变可能导致黑色素瘤突变的一个子集.
科学领域:
- 皮肤病学 皮肤病学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 紫外线B (UVB) 辐射是通过DNA损伤和突变引起皮肤癌的已知诱导因素.
- 黑色素瘤表现出与UVB诱导的环丁二次体 (CPD) 相关的突变特征,但其他特征仍然无法解释.
- 紫外线A (UVA) 辐射在黑色素瘤突变发生中的潜在作用正在研究中.
研究的目的:
- 调查紫外线辐射是否有助于黑色素瘤突变特征.
- 为了比较人类黑色素细胞中UVA和UVB诱导的DNA损伤和突变模式.
主要方法:
- 人类黑色素细胞暴露于UVA (340-400nm) 和UVB (280-320nm).
- 基因组范围内的DNA损伤 (CPDs,8-oxoguanines) 用基本分辨率进行了映射.
- 单个黑色素细胞克隆的全基因组测序确定了突变模式.
主要成果:
- 在TT序列选择性地诱导紫外线CPD,类似于黑色素瘤特征SBS7d.
- 紫外线诱导的CPD没有被发现是致变的.
- 虽然存在8-oxoguanine,但UVA并没有显著增加其水平.
- 与黑色素瘤特征SBS18相匹配的G / C到T / A突变突出,但UVA并没有显著增加.
- 紫外线对人类黑色素细胞具有有限的突变效应.
结论:
- 紫外线辐射会导致黑色素细胞的DNA受损,但具有惊人的有限的直接突变性影响.
- 黑色素细胞中的氧化基损伤可能受到UVA的影响,可能与黑色素瘤突变的一个子集有关.
- 需要进一步的研究来阐明UVA在黑色素瘤发展中的确切作用.
相关概念视频
01:35Mutations
42.9K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
42.9K
01:39Mutations
94.3K
Overview
94.3K
01:38Nucleotide Excision Repair
5.0K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
5.0K
01:08Nucleotide Excision Repair
40.6K
Overview
40.6K
01:30Skin Cancer
5.7K
Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
5.7K
01:30Spontaneous and Induced Mutations
2.1K
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).
2.1K