Sewduth Raj N, Georgelou Konstantina
VIB KU Leuven Center for Cancer Biology, 49 Herestraat, 3000 Leuven, Belgium.
Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), N. Plastira 100, Vasilika Vouton, GR-70013 Heraklion, Greece.
J Xenobiot. 2024 Jan 5;14(1):96-109. doi: 10.3390/jox14010006.
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.
化学物质可通过损伤动物的DNA、使其基因发生突变以及改变其表观遗传特征而导致动物患癌。致癌物诱导的临床前癌症模型对于理解致癌物诱导的人类癌症很有用，因为它们能够重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。然而，这些模型也存在一些局限性，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可能比在人类体内更有效或更具毒性，而且肿瘤在遗传学和表型上可能存在差异。一些化学物质还可能影响正常细胞和组织，比如通过引起氧化应激、炎症和细胞死亡，这可能会改变肿瘤行为和对治疗的反应。此外，一些化学物质的作用可能因暴露条件（如剂量、途径和持续时间）以及动物特征（如遗传学和激素）的不同而有所变化。因此，应谨慎选择、验证和标准化这些模型，并应谨慎解释结果并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征，如遗传和表观遗传变化、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改进它们当前和未来面临的挑战。本综述全面概述了致癌物诱导癌症模型的现状，并为癌症研究提供了新的视角。
