Evidence That Hydrogen Sulfide Is a Genotoxic Agent

Hydrogen sulfide (H 2 S) produced by commensal sulfate-reducing bacteria, which are often members of normal colonic microbiota, represents an environmental insult to the intestinal epithelium potentially contributing to chronic intestinal disorders that are dependent on gene-environment interactions...

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Bibliographic Details
Published in:Molecular cancer research 2006-01, Vol.4 (1), p.9-14
Main Authors: Matias S. Attene-Ramos, Elizabeth D. Wagner, Michael J. Plewa, H. Rex Gaskins
Format: Article
Language:English
Subjects:
Animals
Cell Nucleus - drug effects
CHO Cells
colorectal cancer
Comet Assay
Cricetinae
cytotoxicity
DNA Damage
Genome - drug effects
genotoxicity
HT29 Cells
Humans
hydrogen sulfide
Hydrogen Sulfide - toxicity
Hydroxyurea - pharmacology
inflammatory bowel disease
Mutagens - toxicity
sulfate-reducing bacteria
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Summary:Hydrogen sulfide (H 2 S) produced by commensal sulfate-reducing bacteria, which are often members of normal colonic microbiota, represents an environmental insult to the intestinal epithelium potentially contributing to chronic intestinal disorders that are dependent on gene-environment interactions. For example, epidemiologic studies reveal either persistent sulfate-reducing bacteria colonization or H 2 S in the gut or feces of patients suffering from ulcerative colitis and colorectal cancer. However, a mechanistic model that explains the connection between H 2 S and ulcerative colitis or colorectal cancer development has not been completely formulated. In this study, we examined the chronic cytotoxicity of sulfide using a microplate assay and genotoxicity using the single-cell gel electrophoresis (SCGE; comet assay) in Chinese hamster ovary (CHO) and HT29-Cl.16E cells. Sulfide showed chronic cytotoxicity in CHO cells with a %C1/2 of 368.57 μmol/L. Sulfide was not genotoxic in the standard SCGE assay. However, in a modified SCGE assay in which DNA repair was inhibited, a marked genotoxic effect was observed. A sulfide concentration as low as 250 μmol/L (similar to that found in human colon) caused significant genomic DNA damage. The HT29-Cl.16E colonocyte cell line also exhibited increased genomic DNA damage as a function of Na 2 S concentration when DNA repair was inhibited, although these cells were less sensitive to sulfide than CHO cells. These data indicate that given a predisposing genetic background that compromises DNA repair, H 2 S may lead to genomic instability or the cumulative mutations found in adenomatous polyps leading to colorectal cancer. (Mol Cancer Res 2006;4(1):9–14)
ISSN:1541-7786
1557-3125
DOI:10.1158/1541-7786.MCR-05-0126