致癌物诱导的临床前癌症模型的相关性

IF 6.8 Q1 TOXICOLOGY Journal of Xenobiotics Pub Date : 2024-01-05 DOI:10.3390/jox14010006
R. Sewduth, K. Georgelou
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引用次数: 0

摘要

化学制剂可通过破坏动物的 DNA、使其基因突变和改变其表观遗传特征而导致动物患癌。致癌物诱发的临床前癌症模型有助于了解致癌物诱发的人类癌症,因为它们可以再现肿瘤类型的多样性和复杂性,以及与宿主环境的相互作用。不过,这些模型也有一些缺点,限制了它们的适用性和有效性。例如,某些化学物质在动物体内的效果或毒性可能比在人体内更强,肿瘤的遗传学和表型也可能不同。有些化学物质还可能影响正常细胞和组织,如引起氧化应激、炎症和细胞死亡,从而改变肿瘤的行为和对治疗的反应。此外,一些化学物质可能会因暴露条件(如剂量、途径和持续时间)以及动物特征(如遗传和激素)的不同而产生不同的影响。因此,应慎重选择、验证和标准化这些模型,并谨慎解释其结果和与其他模型进行比较。本综述涵盖了化学诱导癌症模型的主要特点,如遗传和表观遗传学变化、肿瘤环境、血管生成、侵袭和转移以及免疫反应。我们还讨论了这些模型的优缺点以及当前和未来改进这些模型所面临的挑战。这篇综述全面概述了致癌物诱导癌症模型的最新进展,为癌症研究提供了新的视角。
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Relevance of Carcinogen-Induced Preclinical Cancer Models
Chemical agents can cause cancer in animals by damaging their DNA, mutating their genes, and modifying their epigenetic signatures. Carcinogen-induced preclinical cancer models are useful for understanding carcinogen-induced human cancers, as they can reproduce the diversity and complexity of tumor types, as well as the interactions with the host environment. However, these models also have some drawbacks that limit their applicability and validity. For instance, some chemicals may be more effective or toxic in animals than in humans, and the tumors may differ in their genetics and phenotypes. Some chemicals may also affect normal cells and tissues, such as by causing oxidative stress, inflammation, and cell death, which may alter the tumor behavior and response to therapy. Furthermore, some chemicals may have variable effects depending on the exposure conditions, such as dose, route, and duration, as well as the animal characteristics, such as genetics and hormones. Therefore, these models should be carefully chosen, validated, and standardized, and the results should be cautiously interpreted and compared with other models. This review covers the main features of chemically induced cancer models, such as genetic and epigenetic changes, tumor environment, angiogenesis, invasion and metastasis, and immune response. We also address the pros and cons of these models and the current and future challenges for their improvement. This review offers a comprehensive overview of the state of the art of carcinogen-induced cancer models and provides new perspectives for cancer research.
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来源期刊
CiteScore
5.30
自引率
1.70%
发文量
21
审稿时长
10 weeks
期刊介绍: The Journal of Xenobiotics publishes original studies concerning the beneficial (pharmacology) and detrimental effects (toxicology) of xenobiotics in all organisms. A xenobiotic (“stranger to life”) is defined as a chemical that is not usually found at significant concentrations or expected to reside for long periods in organisms. In addition to man-made chemicals, natural products could also be of interest if they have potent biological properties, special medicinal properties or that a given organism is at risk of exposure in the environment. Topics dealing with abiotic- and biotic-based transformations in various media (xenobiochemistry) and environmental toxicology are also of interest. Areas of interests include the identification of key physical and chemical properties of molecules that predict biological effects and persistence in the environment; the molecular mode of action of xenobiotics; biochemical and physiological interactions leading to change in organism health; pathophysiological interactions of natural and synthetic chemicals; development of biochemical indicators including new “-omics” approaches to identify biomarkers of exposure or effects for xenobiotics.
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