Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study

被引：0

作者：

Kaly, Mst. Kusum ^{[1
]}

Rahman, Md Ekhtiar ^{[1
]}

Rana, Md. Sohel ^{[1
]}

Acharjee, Uzzal Kumar ^{[1
]}

Nasirujjaman, Khondokar ^{[1
]}

机构：

[1] Univ Rajshahi, Dept Genet Engn & Biotechnol, Rajshahi 6205, Bangladesh

来源：

SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期

关键词：

N-NITROSODIMETHYLAMINE; RISK; DNA; O-6-METHYLGUANINE; CANCER; ROLES; WATER;

D O I：

10.1038/s41598-024-82984-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14