Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review

Author:

Venkatachalam Karthikkumar1ORCID,Vinayagam Ramachandran2,Arokia Vijaya Anand Mariadoss2,Isa Nurulfiza Mat3,Ponnaiyan Rajasekar4

Affiliation:

1. Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain-17666, United Arab Emirates

2. Department of Biotechnology, Thiruvalluvar University, Serkadu, Vellore, Tamilnadu 632 115, India

3. Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400 Seri Kembangan, Selangor, Malaysia

4. Department of Zoology, Jamal Mohamed College, Tiruchirappalli, Tamil Nadu 620020, India

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Toxicology

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