Monosodium glutamate-induced alterations in MMR protein expression: A potential mechanism linking diet and colorectal cancer

Defective mismatch repair (MMR) proteins activate the microsatellite instability (MSI) pathway, contributing to colon carcinogenesis. Monosodium glutamate (MSG), a widely used flavor enhancer, has been implicated in colorectal cancer (CRC) risk, though the mechanisms remain unclear. This study examines the impact of MSG consumption on the expression of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) proteins in rat colon tissues, which plays crucial role in DNA mismatch repair. The study employed male Wistar rats divided into four groups of six rats each: a control group, a group with N,N-dimethylhydrazine (DMH)-induced CRC (s.c.), and two experimental groups administered different doses (20,000 and 30,000 mg/Kg body weight/day) of MSG orally for four weeks. Immunohistochemistry (IHC) was used to assess MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) protein expression levels in colon tissues. IHC results indicate a dose-dependent reduction in both MLH1 and MSH2 protein expressions in rats exposed to MSG. The reduced MLH1 and MSH2 expressions observed in MSG-exposed rats mirror patterns seen in DMH-induced CRC models, suggesting a potential mechanistic link between MSG intake and CRC development through microsatellite instability (MSI) pathways. The study reveals that MSG affects MLH1 and MSH2 protein expressions, which are vital for DNA mismatch repair, highlighting a potential mechanism by which MSG may influence microsatellite instability and CRC development. These findings underscore the need for further research to clarify the implications of MSG consumption for CRC risk and to identify potential molecular targets and dietary recommendations for prevention. • Food additives implicated in colorectal cancer risk. • MSG reduces MLH1 and MSH2 expression in Colon tissues. • MMR protein loss linked to β-catenin translocation in CRC. • MSG exposure impairs DNA repair, increasing MSI risk. • Wnt pathway dysregulation associated with CRC progression.