Purpose: Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs.
Materials and Methods: Conventional domestic swine (Sus scrofa domesticus) were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis.
Results: Ten swine (seven males, three females; age: 2 months; weight: 9– 15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162– 228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15– 22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma.
Conclusion: This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.

Keywords: carcinogenesis, large animal model, hepatocellular carcinoma, domestic swine, DENA induction


中文翻译：

---

N-二乙基亚硝胺和苯巴比妥诱导传统家猪肝癌

目的：大型动物模型由于与人类相似，仍在许多研究中使用。目前尚无文献记载，通常为肉类生产而饲养的常规体型的传统农场猪可用于生成肝细胞癌 (HCC) 动物模型。本研究的目的是调查 N-二乙基亚硝胺 (DENA) 和苯巴比妥 (PB) 一起如何在普通养殖猪中产生 HCC。
材料和方法：使用传统家猪（Sus scrofa Domesticus ）。 DENA 15 mg/kg 每周腹腔注射，持续 12 周，而 PB 片剂 (4 mg/kg) 也通过食物给药，持续 16 周。进行血液检测和超声检查评估以监测进展。随后，对疑似结节的病例进行计算机断层扫描，然后进行组织病理学检查以确诊。
结果：研究对象包括 10 头猪（7 只雄性，3 只雌性；年龄：2 个月；体重：9-15 kg），并随访 25 个月；九个是实验性的，一个是出于道德考虑的对照。本研究期间动物的最大体重达到162-228公斤。干预猪的体重增加明显低于对照猪的体重增加。实验室分析显示肝功能标志物没有明显异常，但尿素（p = 0.028）和肌酐（p = 0.003）水平确实显示出统计学上的显着变化。超声检查和计算机断层扫描显示多个肝脏结节，其特征类似于 HCC。系列成像筛查和更广泛的观察表明，所有动物最终都出现了肿瘤。诱导后 15-22 周的组织病理学证实显示，所有接受干预的猪都出现了多个分化良好的 HCC 结节，有些还出现了肝血管肉瘤。
结论：本研究通过 DENA 和 PB 组合成功地在传统家猪中产生了 HCC。这项调查至少需要15个月才能形成肿瘤。该模型将有利于未来大型动物肝癌的研究。

关键词:致癌作用, 大动物模型, 肝细胞癌, 家猪, DENA诱导