Evidence that hydrogen sulfide is a genotoxic agent

Area of Science:

• Gastroenterology
• Molecular Biology
• Toxicology

Background:

• Commensal sulfate-reducing bacteria produce hydrogen sulfide (H2S) in the colon.
• H2S is implicated in chronic intestinal disorders like ulcerative colitis and colorectal cancer.
• A clear mechanistic link between H2S and these diseases is lacking.

Purpose of the Study:

• To investigate the chronic cytotoxicity and genotoxicity of sulfide in intestinal cell models.
• To explore the role of DNA repair inhibition in sulfide-induced genotoxicity.

Main Methods:

• Cytotoxicity assessed using a microplate assay in Chinese hamster ovary (CHO) and HT29-Cl.16E cells.
• Genotoxicity evaluated using the single-cell gel electrophoresis (SCGE; comet assay) with and without DNA repair inhibition.
• Sulfide concentrations relevant to the human colon were tested.

Main Results:

• Sulfide demonstrated chronic cytotoxicity in CHO cells.
• Sulfide was not genotoxic in standard SCGE assays but showed significant genomic DNA damage when DNA repair was inhibited.
• A sulfide concentration of 250 micromol/L, found in the human colon, caused substantial DNA damage in the presence of inhibited repair.
• HT29-Cl.16E colonocytes also showed DNA damage with inhibited repair, though less sensitive than CHO cells.

Conclusions:

• Sulfide can cause genomic DNA damage, particularly when DNA repair mechanisms are compromised.
• This genotoxic effect, under conditions of impaired DNA repair, may contribute to genomic instability and mutations driving colorectal cancer development.
• H2S represents a potential environmental factor in gene-environment interactions leading to colorectal cancer.