title: Suppression of endogenous hydrogen sulfide contributes to the radiation-induced bystander effects on hypoxic HepG2 cells.
abstract: Radiation-induced bystander effects may have important implications in radiotherapy, but it is still not well known if radiation-induced bystander effects can be triggered in hypoxic tumor cells and what are the related bystander signals. Using human hepatoma cells of HepG2, the present study found that micronuclei (MN) could be induced in the nonirradiated cells after treatment with conditioned medium (CM) harvested from irradiated cells under hypoxic conditions. Bystander effects were diminished when the irradiated cells were pretreated with sodium hydrosulfide (NaHS, an exogenous H(2)S donor) (≤100 μM). However, the bystander effects were increased when the irradiated cells were pretreated with an inhibitor of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the synthases of endogenous hydrogen sulfide (H(2)S). Western blotting showed that the expressions of CSE and CBS were increased in the irradiated hypoxic cells, but were reduced in the CM treated bystander cells. The ratio of Bcl-2/Bax, a molecular marker of apoptosis, decreased with CM treatment time. However, the activity of caspase-3 increased in the hypoxic bystander cells, and this could be regulated by both NaHS and the inhibitor of endogenous H(2)S. These results demonstrate that under hypoxic conditions irradiated hepatoma cells induce bystander responses by depressing the generation of endogenous H(2)S and altering Bcl-2/Bax ratios as well as caspase-3 dependent damage in the bystander cells.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Xie
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Xu
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D024201:Bystander Effect; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects; D005720:Gamma Rays; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D056945:Hep G2 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors / Q000378:metabolism; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D019253:Proto-Oncogene Proteins c-bcl-2; D013440:Sulfides; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide