No difference in 4-nitroquinoline induced tumorigenesis between germ-free and colonized mice.

Abstract:

:Variations in oral bacterial communities have been linked to oral cancer suggesting that the oral microbiome is an etiological factor that can influence oral cancer development. The 4-nitroquinoline 1-oxide (4-NQO)-induced murine oral and esophageal cancer model is frequently used to assess the effects of preventive and/or therapeutic agents. We used this model to assess the impact of the microbiome on tumorigenesis using axenic (germ-free) and conventionally housed mice. Increased toxicity was observed in germ-free mice, however, no difference in tumor incidence, multiplicity, and size was observed. Transcriptional profiling of liver tissue from germ-free and conventionally housed mice identified 254 differentially expressed genes including ten cytochrome p450 enzymes, the largest family of phase-1 drug metabolizing enzymes in the liver. Gene ontology revealed that differentially expressed genes were enriched for liver steatosis, inflammation, and oxidative stress in livers of germ-free mice. Our observations emphasize the importance of the microbiome in mediating chemical toxicity at least in part by altering host gene expression. Studies on the role of the microbiome in chemical-induced cancer using germ-free animal models should consider the potential difference in dose due to the microbiome-mediated changes in host metabolizing capacity, which might influence the ability to draw conclusions especially for tumor induction models that are dose dependent.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Zhou YX,Fuentes-Creollo G,Ponce F,Langley SA,Jen KY,Celniker SE,Mao JH,Snijders AM

doi

10.1002/mc.22972

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

627-632

issue

5

eissn

0899-1987

issn

1098-2744

journal_volume

58

pub_type

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