Chemical Carcinogen (3-Methylcholanthrene)-induced Pleomorphic Rhabdomyosarcomas in Fanconi Anemia Fancd2-/-, Fancg-/- (C57BL/6), Fancd2-/- (129/Sv) Mice.

IF 1.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL In vivo Pub Date : 2024-11-01 DOI:10.21873/invivo.13734

Renee Fisher, Michael W Epperly, Lora H Rigatti, Donna Shields, Joel S Greenberger, Anthony Green, Amitava Mukherjee

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Abstract

Background/aim: Radiation oncologists are reluctant to treat cancer in Fanconi Anemia (FA) patients due to their lack of homologous recombination repair of DNA strand breaks in normal tissues. To determine the therapeutic effects of irradiation and combination chemotherapy on cancer in syngeneic, radiosensitive FA mice, we derived transplantable cancers of the same genotype in three FA mouse strains.

Materials and methods: Fancd2-/- mice on a C57BL/6 or Sv/129 background and Fancg-/- mice (C57BL/6 background) that received 3-methylcholanthrene (3-MCA), were monitored for the development of subcutaneous tumors.

Results: Tumors were induced at the site of 3-MCA injection, and tumor cell lines were established and found to be transplantable. Explanted tumors were identified as pleomorphic/rhabdomyosarcomas using immunohistochemical biomarkers.

Conclusion: These transplantable FA mouse tumor cell lines should be valuable for testing effects of new radiation therapy protocols including FLASH high dose rate radiation delivery, immunotherapies, and combined radiation and chemotherapy treatments for radiosensitive FA patients.

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化学致癌物（3-甲基胆蒽）诱导范可尼贫血症 Fancd2-/-、Fancg-/- (C57BL/6)、Fancd2-/- (129/Sv) 小鼠发生多形性横纹肌肉瘤。

背景/目的：由于范可尼贫血症（FA）患者缺乏正常组织中DNA链断裂的同源重组修复功能，放射肿瘤学家不愿意对其进行癌症治疗。为了确定辐照和联合化疗对辐射敏感的FA小鼠癌症的治疗效果，我们在三个FA小鼠品系中衍生出了相同基因型的可移植癌症：观察C57BL/6或Sv/129背景的Fancd2-/-小鼠和接受3-甲基胆蒽（3-MCA）治疗的Fancg-/-小鼠（C57BL/6背景）的皮下肿瘤发生情况：结果：在注射 3-MCA 的部位诱发了肿瘤，并建立了肿瘤细胞系，发现它们可以移植。用免疫组化生物标记物鉴定出取出的肿瘤为多形性/横纹肌肉瘤：结论：这些可移植的FA小鼠肿瘤细胞系对测试新的放射治疗方案（包括FLASH高剂量率放射治疗、免疫疗法以及针对放射敏感性FA患者的放化疗联合疗法）的效果很有价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

In vivo 医学-医学：研究与实验

CiteScore

4.20

自引率

4.30%

发文量

330

审稿时长

3-8 weeks

期刊介绍： IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management. The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.