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牛眼鳞状细胞癌中DNA损伤与细胞凋亡的研究

Investigation of DNA Damage and Apoptosis in Bovine Ocular Squamous Cell Carcinoma.

作者信息

Dörtbudak Muhammet Bahaeddin, Yener Kerem

机构信息

Faculty of Veterinary Medicine, Department of Pathology, Harran University, Şanlıurfa, Turkey.

Faculty of Veterinary Medicine, Department of Surgery, Harran University, Şanlıurfa, Turkey.

出版信息

Vet Med Sci. 2025 Jul;11(4):e70448. doi: 10.1002/vms3.70448.

Abstract

Ocular squamous cell carcinoma represents the most prevalent form of cancer in cattle and exerts a deleterious effect on animal welfare and breeders. This study sought to elucidate the relationship between DNA damage and apoptosis with the aim of advancing our understanding of the pathogenesis of the disease. Nine bovine tissue samples with suspected ocular squamous cell carcinoma (OSCC) were examined histopathologically and immunohistochemically. The taken tissue samples, in histopathological examinations by haematoxylin-eosin (HE), staining revealed the presence of neoplastic cells exhibiting various grades of differentiation. It observed the presence of polygonal or ovoid-shaped cells with hyperchromatic nuclei and vesicular cytoplasm, as well as mitotic figures and bizarre giant cells. Islets and caudal extensions of the tumour cells were observed to contain keratin deposits. Immunohistochemical staining of OSCC tissues was performed using γ-H2AX for DNA double-strand breaks, 8-OHdG for DNA oxidation and CASP-3 biomarkers for nuclear apoptosis. The immunohistochemical examination demonstrated that the expression of 𝛾-H2AX and 8-OHdG was markedly elevated, while CASP-3 expression was relatively diminished in aggressive tumours. In contrast, the opposite was observed in low-grade tumours. This study is the first to report DNA double-stranded breaks in eye cancers, and it has also shown that DNA helix breaks and guanine oxidation are effective in cancer pathogenesis. It has also been determined that apoptotic defence reactions due to DNA damage are reduced. In light of these findings, we made a significant contribution to the development of BOSCC carcinogenesis.

摘要

眼鳞状细胞癌是牛中最常见的癌症形式,对动物福利和养殖者产生有害影响。本研究旨在阐明DNA损伤与细胞凋亡之间的关系,以增进我们对该疾病发病机制的理解。对9个疑似眼鳞状细胞癌(OSCC)的牛组织样本进行了组织病理学和免疫组织化学检查。所取组织样本在苏木精-伊红(HE)组织病理学检查中,染色显示存在呈现不同分化程度的肿瘤细胞。观察到存在具有深染细胞核和泡状细胞质的多边形或卵圆形细胞,以及有丝分裂象和奇异的巨细胞。观察到肿瘤细胞的岛状和尾状延伸含有角蛋白沉积物。使用γ-H2AX检测DNA双链断裂、8-OHdG检测DNA氧化以及CASP-3生物标志物检测核凋亡,对OSCC组织进行免疫组织化学染色。免疫组织化学检查表明,在侵袭性肿瘤中,γ-H2AX和8-OHdG的表达明显升高,而CASP-3表达相对降低。相反,在低级别肿瘤中观察到相反的情况。本研究首次报道了眼癌中的DNA双链断裂,并且还表明DNA螺旋断裂和鸟嘌呤氧化在癌症发病机制中起作用。还确定了由于DNA损伤引起的凋亡防御反应减少。鉴于这些发现,我们对牛眼鳞状细胞癌(BOSCC)致癌作用的发展做出了重大贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5658/12199710/9f54c86539a9/VMS3-11-e70448-g002.jpg

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