Objective: N-Nitrosodimethylamine (NDMA), a well-known environmental carcinogen, has been implicated in the etiology of colorectal cancer (CRC). However, the precise molecular mechanisms underlying its carcinogenic effects remain incompletely understood. This study employs an integrated approach combining network toxicology and molecular docking to systematically identify key molecular targets and signaling pathways involved in NDMA-induced CRC. Methods: ADMETlab 2.0 and ProTox-II software were employed to predict the toxicological properties of N-Nitrosodimethylamine. By integrating data from the Genecards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM) databases, a set of overlapping target genes associated with both NDMA exposure and colorectal cancer was identified. The STRING database was utilized to construct a protein-protein interaction (PPI) network, and core targets were screened using Cytoscape software. Functional enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed via the Metascape platform. Finally, molecular docking simulations were conducted using CB-Dock software to calculate binding free energies. Results: Predictions by ADMETlab 2.0 and ProTox-II indicated that NDMA exhibits significant carcinogenicity, and 111 overlapping target genes between NDMA and CRC were identified. PPI network analysis revealed 57 core targets, with TP53, ACTB, EZH2, TNF, and HDAC1 identified as hub targets (exhibiting the highest degree values). GO and KEGG enrichment analyses demonstrated that these target genes are primarily involved in biological processes such as chromatin remodeling, rhythmic processes, regulation of protein modification processes, and regulation of the MAPK cascade. They are participat in the regulation of signaling pathways such as Lysine degradation, Pathways in cancer, Transcriptional misregulation in cancer, TGF-beta signaling pathway, and Antigen processing and presentation. Conclusions: N-Nitrosodimethylamine is highly associated with the pathogenesis of CRC, with TP53, ACTB, EZH2, TNF, and HDAC1 identified as potential key targets. This study provides critical theoretical insights into the role of NDMA in CRC pathogenesis.

N-Nitrosodimethylamin, Colorectal Cancer, Network Toxicology, Molecular Docking