Immunohistochemical Analysis of Tumor Suppressor p53 in p-Dimethylamino Benzaldehyde (DMBA) Induced Hepatocarcinogenesis in Rats (Rattus norvegicus L.) Male Wistar Strains

Aims: Hepatocellular carcinoma accounts for approximately 90% of all primary liver malignancies and poses a major global health challenge. The initiation of hepatocellular carcinoma (HCC) is marked by a progressive accumulation of molecular alterations, the origins of which remain largely unclear. This study provides an extensive immunohistochemical analysis of hepatitis, cirrhosis, and HCC using a p-Dimethylamino Benzaldehyde (DMBA)-induced HCC rats model. p-Dimethylamino benzaldehyde (DMBA) is a common environmental polycyclic aromatic hydrocarbon, acting as a mutagen, capable of exerting carcinogenic effects, which can be tested both in cell culture and in vivo animal models.
Study Design: This study used an in vivo laboratory test method.
Place and Duration of Study: Department of Pharmacology and Therapy and Department of Histology, Faculty of Medicine, Udayana University, between December 2023 to July 2024.
Methodology: This study used an in vivo laboratory test method. The laboratory test was in the form of a study on experimental animals, Wistar rats induced by p -Dimethylamino Benzaldehyde (DMBA) treatment. Observation of Hepatocellular Carcinoma in rat liver tissue samples with immunohistochemical tests of expression Tumor Suppressor p53 in tumor and non-tumor hepatocytes.
Results: The results of the hypothesis test study on tumor diameter and immunohistochemical test on the expression of Tumor Suppressor p53 with ROC analysis showed that the cut off tumor diameter obtained a cutoff value of 0.5 with a sensitivity value of 1.0 and a specificity value of 1.0. The results of the ROC analysis showed that the H-score data of wild-type p53 Immunohistochemistry contained 26 samples with 7 positive HCC results and 19 negative samples.
Conclusion: This study shows that in male Wistar rats p-Dimethylamino benzaldehyde (DMBA) -induced hepatocarcinogenesis can be a viable model for studying Hepatocellular Carcinoma in the future.

研究目的：肝细胞癌约占所有原发性肝癌的90%，对全球公共卫生构成重大挑战。肝细胞癌（HCC）的起始特征为分子改变的逐渐累积，其起源尚不清楚。本研究通过对由p-二甲基氨基苯甲醛（DMBA）诱导的肝细胞癌大鼠模型进行的广泛免疫组化分析，对肝炎、肝硬化及肝细胞癌进行了深入研究。p-二甲基氨基苯甲醛（DMBA）是一种常见的环境多环芳烃，作为一种诱变剂，能够发挥致癌效应，可在细胞培养和体内动物模型中进行检测。
研究设计：本研究采用体内实验室检测方法。
研究地点及持续时间：乌达亚纳大学医学院药理学与治疗学部及组织学部，研究时间为2023年12月至2024年7月。
研究方法：本研究采用体内实验室检测方法。实验室检测以实验动物研究的形式进行，即用p-二甲基氨基苯甲醛（DMBA）处理的Wistar大鼠。
结果：对肿瘤直径进行假设检验研究以及对肿瘤抑制蛋白p53在肿瘤和非肿瘤肝细胞中的表达进行免疫组化检测，并采用ROC分析，结果显示，所获得的截止肿瘤直径的截止值为0.5，灵敏度和特异性均为1.0。ROC分析结果显示，野生型p53免疫组化H-score数据包含26个样本，其中7个样本为阳性HCC结果，19个样本为阴性样本。
结论：本研究表明，在雄性Wistar大鼠中，p-二甲基氨基苯甲醛（DMBA）诱导的肝细胞癌发生可以作为未来研究肝细胞癌的可行模型。