Venkatachalam Karthikkumar, Vinayagam Ramachandran, Arokia Vijaya Anand Mariadoss, Isa Nurulfiza Mat, Ponnaiyan Rajasekar
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain-17666, United Arab Emirates.
Department of Biotechnology, Thiruvalluvar University, Serkadu, Vellore, Tamilnadu 632 115, India.
Toxicol Res (Camb). 2020 Mar 30;9(1):2-18. doi: 10.1093/toxres/tfaa004. eCollection 2020 Feb.
1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.
1,2 - 二甲基肼(DMH)是肼类的一种,是一种强DNA烷基化剂,天然存在于苏铁科植物中。DMH被广泛用作致癌物,在动物模型中诱导结肠癌。在啮齿动物模型中探索DMH诱导的结肠癌发生,有助于了解结肠癌发生不同阶段的生化、分子和组织学机制。前致癌物DMH经过一系列代谢反应后最终到达结肠,在那里产生最终致癌物和活性氧(ROS),后者进一步使DNA烷基化并启动结肠癌发生的进程。DMH诱导的结肠肿瘤的癌前病变和组织病理学观察可能为了解啮齿动物和人类的这种疾病提供典型依据。此外,本综述讨论了参与DMH中毒的生物转化和抗氧化酶的作用。这种认识对于在评估DMH诱导的动物结肠癌发生过程中的天然或药理化合物时,准确识别和解释结肠黏膜中发生的变化至关重要。