Mitochondrial Complex I Molecular alterations in Sapajus apella as a human gastric carcinogenesis model after MNU exposure

Abstract

Introduction: Gastric cancer (GC) remains among the top five global health problems. Therefore, comprehending the tumor energetic behavior is critical to understanding its progression. This study aimed to investigate mitochondrial DNA (mtDNA) alterations in GC cancer cell lines in an animal model. Material and Methods: Four mitochondrial genes (COI, ATP8, ND1, and ND3) were analyzed in GC (AGP01, ACP02, ACP03, and PG100) and control (Walker 256 carcinosarcoma) cell lines inoculated in Sapajus apella, exposed and not exposed to N-methyl-N-nitrosourea. Results: Two synonymous alterations were identified in ND1. In ND3, a non-synonymous alteration (A10398G ➔ Thr114Ala) may decrease the respiratory chain Complex I efficiency, enhancing cellular reactive oxygen species and contributing to mtDNA damage. As alterations in ND1 and ND3 were observed in highly aggressive cell lines, our results suggest these genes may play crucial roles in energetic efficiency and gastric carcinogenesis.