Mitochondrial Complex I Molecular Alterations in Sapajus apella as a Human Gastric Carcinogenesis Model After MNU Exposure

IF 0.8 4区农林科学 Q3 VETERINARY SCIENCES

Journal of Medical Primatology Pub Date : 2025-04-01 DOI:10.1111/jmp.70017

Bárbara dos Santos Dias, Symara Rodrigues Antunes, Danilo do Rosário Pinheiro, Rommel Mario Rodriguez Burbano, Bárbara do Nascimento Borges

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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.

Abstract Image

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MNU暴露后无骨参线粒体复合体I分子的改变

导言胃癌（GC）仍然是全球五大健康问题之一。因此，了解肿瘤的能量行为对于理解其进展至关重要。本研究旨在研究动物模型中 GC 癌细胞系的线粒体 DNA（mtDNA）改变。材料与方法分析了接种于 Sapajus apella、暴露于或未暴露于 N-甲基-N-亚硝基脲的 GC（AGP01、ACP02、ACP03 和 PG100）细胞系和对照（Walker 256 cancerosarcoma）细胞系中的四个线粒体基因（COI、ATP8、ND1 和 ND3）。结果在 ND1 中发现了两个同义变化。在 ND3 中，一个非同义改变（A10398G ➔ Thr114Ala）可能会降低呼吸链复合物 I 的效率，增加细胞活性氧并导致 mtDNA 损伤。由于在高侵袭性细胞系中观察到了 ND1 和 ND3 的改变，我们的结果表明这些基因可能在能量效率和胃癌发生中起着关键作用。

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来源期刊

Journal of Medical Primatology 生物-动物学

CiteScore

1.40

自引率

42.90%

发文量

审稿时长

6 months

期刊介绍： The Journal of Medical Primatology publishes research on non-human primates as models to study, prevent, and/or treat human diseases; subjects include veterinary medicine; morphology, physiology, reproductive biology, central nervous system, and cardiovascular diseases; husbandry, handling, experimental methodology, and management of non-human primate colonies and laboratories; non-human primate wildlife management; and behaviour and sociology as related to medical conditions and captive non-human primate needs. Published material includes: Original Manuscripts - research results; Case Reports - scientific documentation of a single clinical study; Short Papers - case histories, methodologies, and techniques of particular interest; Letters to the Editor - opinions, controversies and sporadic scientific observations; Perspectives – opinion piece about existing research on a particular topic; Minireviews – a concise review of existing literature; Book Reviews by invitation; Special Issues containing selected papers from specialized meetings; and Editorials and memoriams authored by the Editor-in-Chief.