与p53介导的细胞循环途径相关的Halobenzoquinone诱导的潜在致癌性
Qing Zhong1, Yuwen Huang1, Yujie Sha1
1Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Environmental pollution (Barking, Essex : 1987)
|November 3, 2024
概括
两个新兴的基 (HBQs),2,6-二-1,4-基和2,6-二-1,4-基,显示出潜在的致癌性. 这些化合物诱导细胞损伤和恶性转变,影响p53细胞循环路径.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 在饮用水中经常检测到新兴的基 (HBQ),特别是2,6-二-1,4-基 (2,6-DBBQ) 和2,6-二-1,4-基 (2,6-DCBQ).
- 这些HBQ的毒性高于监管消毒副产品,预计是潜在的膀致癌物,但缺乏直接致癌证据和机制性见解.
研究的目的:
- 通过实验证实2,6-DBBQ和2,6-DCBQ的潜在致癌性.
- 评估这些HBQs的细胞毒性和基因毒性.
- 调查潜在的毒性机制,包括对细胞循环调节和DNA损伤的影响.
主要方法:
- 在体外恶性转化试验,使用人类尿表皮细胞SV-HUC-1细胞.
- 对SV-HUC-1和HepG2细胞的细胞毒性和基因毒性评估.
- 转录组测序分析受2,6-DBBQ和2,6-DCBQ影响的分子通路.
主要成果:
- 2,6-DBBQ和2,6-DCBQ显著降低了细胞活力,并在测试细胞系中诱导了DNA和染色体损伤.
- 暴露于这些HBQs时观察到SV-HUC-1细胞的恶性转化.
- 转录组分析显示了p53介导的细胞循环途径的激活,通过p53下调和p21上调导致S相停止.
结论:
- 这项研究首次实验证实了2,6-DBBQ和2,6-DCBQ的潜在致癌性.
- 这些发现突出了活性氧物种在调解这些HBQs引起的DNA和染色体损伤中的作用.
- 这些结果为HBQs的细胞毒性和基因毒性机制提供了关键的见解,为饮用水污染物的风险评估提供了信息.
相关概念视频
02:37DNA Damage can Stall the Cell Cycle
9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:23Negative Regulator Molecules
35.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
01:31The Intrinsic Apoptotic Pathway
6.4K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
01:27Molecular Factors Affecting Cell Division
3.0K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.0K
01:19Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K