Related Experiment Video
Updated: Jul 18, 2026
High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells
Rajamanickam Baskar1, Ling Li, Philip Keith Moore
1Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 18 Medical Dr., Singapore 117597.
Abstract:
Hydrogen sulfide (H2S) has been shown previously to exert proapoptotic activity. However, the mechanism(s) by which H2S affects cell growth and function have not been addressed adequately. In this study, cultured human lung fibroblasts were treated with the H2S donor NaHS (10-75 microM; 12-48 h). NaHS caused a concentration-dependent increase in micronuclei formation (indicating DNA damage) and cell cycle arrest (G1 phase). NaHS increased expression of ku 70 and ku 80 but did not affect the expression of other DNA repair proteins such as proliferating cell nuclear antigen (PCNA) or replication protein A (rNase protection assay). NaHS treatment also resulted in stabilization of p53 coupled with induction of downstream proteins such as p21, Bax, and cytochrome c, as well as translocation of Bax from the cytosol to the mitochondria and release of cytochrome c from mitochondria. NaHS did not up-regulate cell levels of the antiapoptotic protein, Bcl-2. We propose that the genotoxic action of H2S propels the cell toward apoptotic death triggered initially by stabilization of p53 and subsequently involving a cascade of downstream products. These results are of significance as they uncover a hitherto unknown and very fundamental role for H2S in determining cell fate.
Insights
Hydrogen sulfide (H2S) causes DNA damage and cell cycle arrest in human lung fibroblasts. This genotoxic action triggers apoptosis through p53 stabilization and downstream signaling, revealing a fundamental role for H2S in cell fate determination.
Area of Science:
- Cell Biology
- Toxicology
- Biochemistry
Background:
- Hydrogen sulfide (H2S) is known to have proapoptotic effects.
- The precise mechanisms by which H2S influences cell growth and function remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying H2S-induced apoptosis in human lung fibroblasts.
- To investigate the impact of H2S on DNA damage, cell cycle progression, and apoptotic pathways.
Main Methods:
- Cultured human lung fibroblasts were treated with the H2S donor, sodium hydrosulfide (NaHS).
- Assays were performed to assess micronuclei formation, cell cycle distribution, DNA repair protein expression (Ku 70/80, PCNA), p53 stabilization, and apoptotic markers (Bax, cytochrome c, Bcl-2).
Main Results:
- NaHS induced a concentration-dependent increase in DNA damage (micronuclei formation) and G1 phase cell cycle arrest.
- NaHS treatment led to increased expression of Ku 70/80, p53 stabilization, and induction of proapoptotic proteins (p21, Bax, cytochrome c).
- Bax translocation to mitochondria and cytochrome c release were observed, without affecting Bcl-2 levels.
Conclusions:
- The genotoxic effects of H2S initiate an apoptotic cascade, involving p53 stabilization and downstream signaling.
- H2S plays a critical role in determining cell fate by inducing apoptosis through DNA damage and mitochondrial pathways.
Related Concept Videos
01:30Spontaneous and Induced Mutations
01:35Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
02:26Preparation and Reactions of Sulfides