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Published on: December 19, 2019
Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT
Mst Kusum Kaly1, Md Ekhtiar Rahman1, Md Sohel Rana1
1Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Abstract:
This study investigated the potential genotoxic and carcinogenic effects of N-nitrosodimethylamine (NDMA), a hazardous compound found in ranitidine formulations that are used to treat excessive stomach acid. The study first examined the effects of NDMA-contaminated ranitidine formulation on Allium cepa root growth and mitotic activity. The results demonstrated dose-dependent decreases in both root growth and mitotic index indicating genotoxicity and cell division disruption. Elevated concentrations of ranitidine correlated with increased chromosomal aberrations indicating genotoxic capabilities. These outcomes underscored that NDMA contaminated ranitidine exposure triggers genotoxicity hampering cell division and inducing chromosomal aberrations. Electronic characteristics of NDMA revealed its electrophilic nature suggesting its capability to create covalent adducts with DNA bases fostering genotoxic and carcinogenic characteristics. Molecular docking analysis showed the interactions of NDMA with DNA including hydrogen bonds and carbon-hydrogen interactions with nucleotide bases forming DNA adducts. Molecular dynamics simulations showcased the dynamic behavior of the DNA-NDMA complex over time with structural fluctuations. Dynamic hydrogen bond fluctuations implied interactive intricacies between solute and solvent molecules. Overall, this study illuminates how NDMA-contaminated ranitidine could trigger DNA damage and potentially contribute to carcinogenesis. It emphasizes the urgency of minimizing exposure to this perilous and hazardous compound.
Insights
N-nitrosodimethylamine (NDMA) in ranitidine causes DNA damage and chromosomal aberrations in plant cells, indicating genotoxic and carcinogenic potential. Minimizing exposure to this hazardous compound is crucial.
Area of Science:
- Toxicology
- Molecular Biology
- Genetics
Background:
- Ranitidine formulations have been found to contain N-nitrosodimethylamine (NDMA).
- NDMA is a known hazardous compound with potential genotoxic and carcinogenic effects.
- Excess stomach acid is commonly treated with ranitidine.
Purpose of the Study:
- To investigate the genotoxic and carcinogenic effects of NDMA-contaminated ranitidine.
- To examine the impact of NDMA on cellular processes like root growth and mitosis.
- To elucidate the molecular mechanisms underlying NDMA-induced DNA damage.
Main Methods:
- Allium cepa root growth and mitotic activity assays were performed.
- Chromosomal aberration analysis was conducted.
- Computational methods including electronic characteristic analysis, molecular docking, and molecular dynamics simulations were employed.
Main Results:
- NDMA-contaminated ranitidine exhibited dose-dependent inhibition of root growth and mitotic index in Allium cepa.
- Increased chromosomal aberrations were observed with elevated NDMA concentrations, confirming genotoxicity.
- Molecular simulations revealed NDMA's electrophilic nature and its ability to form DNA adducts through interactions with nucleotide bases.
Conclusions:
- NDMA contamination in ranitidine induces genotoxicity, disrupts cell division, and causes chromosomal damage.
- The electrophilic nature of NDMA facilitates DNA adduct formation, contributing to its carcinogenic potential.
- This study highlights the risks associated with NDMA-contaminated ranitidine and the need for exposure reduction.
