Lead‐Induced Differential Gene Expression and Its Association With Repair Impairment and Tumor Development– An In Silico Analysis

ABSTRACT This study investigates the role of lead toxicity in carcinogenesis by analyzing genetic and molecular mechanisms using computational methods. Researchers identified four core genes ( FUS , NAMPT , RBBP4 , WEE1 ) that interact with DNA repair proteins (PARP1, XRCC5, XRCC6, BRCA1) using functional enrichment techniques, STRING‐based protein networks, and GEO microarray datasets. COSMIC identified 62 nsSNPs in these genes linked to cancer; mutations in these genes may destabilize proteins and prevent DNA repair, which, over time, may promote cancer‐related traits. Lead had a strong binding affinity to these targets, according to protein–metal docking simulations, even though six curcumin derivatives from Curcuma species (bisacurone, EF31, UBS109, and compounds 3/88/91) showed protective benefits by stabilizing wild‐type and mutant proteins. Using GROMACS and molecular dynamics, compounds 88 ( Curcuma caesia ) and UBS109 ( Curcuma longa ) were identified as promising candidates for mitigating lead‐induced dysfunction. According to this study, curcumin derivatives are useful stabilizers of proteins targeted by lead, providing a novel approach to reducing the carcinogenicity associated with heavy metals.