Open AccessEffects of Gut Microbiome on Carcinogenic DNA Damage
Author(s) -
Yun-Chung Hsiao,
Youfu Li,
Liang Chi,
Yifei Yang,
Kun Lü
Publication year - 2020
Publication title -
chemical research in toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 156
eISSN - 1520-5010
pISSN - 0893-228X
DOI - 10.1021/acs.chemrestox.0c00142
Subject(s) - endogeny , dna damage , dna adduct , carcinogenesis , microbiome , carcinogen , oxidative stress , chemistry , dna , biochemistry , lipid peroxidation , colorectal cancer , biology , cancer research , cancer , microbiology and biotechnology , genetics , gene
The human intestine is host to a vast microbial community: the gut microbiome (GM). The GM has been considered as a key modulator of human health in the past decade. In particular, several studies have supported that altered GM is associated with cancer, such as colorectal cancer, adenocarcinoma, and pancreatic cancer. The formation of a DNA adduct is one of the key events in carcinogenesis, and whether GM can influence DNA adducts has yet to be examined. This study analyzed 10 DNA adducts (N 2 -Me-dG, N 6 -Me-dA, N 2 -Et-dG, OH-Me-dG, OH-Me-dA, N 2 -EtD-dG, O 6 -Me-dG, 1,N 2 -ε-dG, 8-oxo-dG, and 5-Cl-dC), attributed to various endogenous processes and physiological stressors, using highly sensitive LC-MS/MS in germ-free (GF) and conventionally raised (CONV-R) mice. Our results showed that significant differences in specific DNA adducts appeared in liver, colon, and small intestine samples between GF and CONV-R mice. The differences in adduct levels may indicate that GM can locally or systemically regulate endogenous processes including neutrophil bactericidal activity (represented by 5-Cl-dC), lipid peroxidation (1,N 2 -ε-dG), oxidative stress generation (8-oxo-dG), and endogenous aldehyde metabolism (OH-Me-dA). Further studies are warranted to elucidate how the GM influences endogenous process, DNA damage, and the risks of developing cancer.