Microvesicles Contribute to the Bystander Effect of DNA Damage

Genotoxic treatments elicit DNA damage response (DDR) not only in cells that are directly exposed but also in cells that are not in the field of treatment (bystander cells), a phenomenon that is commonly referred to as the bystander effect (BE). However, mechanisms underlying the BE remain elusive....

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Bibliographic Details
Published in:International journal of molecular sciences 2017-04, Vol.18 (4), p.788-788
Main Authors: Lin, Xiaozeng, Wei, Fengxiang, Major, Pierre, Al-Nedawi, Khalid, Al Saleh, Hassan A, Tang, Damu
Format: Article
Language:English
Subjects:
Annexin V
Ataxia
Ataxia telangiectasia
Ataxia telangiectasia mutated protein
Ataxia Telangiectasia Mutated Proteins - metabolism
Bystander Effect
Cell Line, Tumor
Deoxyribonucleic acid
DNA
DNA Damage
Etoposide
Etoposide - pharmacology
Exposure
Extracellular Vesicles - physiology
Genotoxicity
Histone H2A
Histones - metabolism
Humans
Male
Phosphorylation
Pretreatment
Prostate cancer
Serine
Signal Transduction
Ultraviolet
Ultraviolet radiation
Ultraviolet Rays
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Summary:Genotoxic treatments elicit DNA damage response (DDR) not only in cells that are directly exposed but also in cells that are not in the field of treatment (bystander cells), a phenomenon that is commonly referred to as the bystander effect (BE). However, mechanisms underlying the BE remain elusive. We report here that etoposide and ultraviolet (UV) exposure stimulate the production of microvesicles (MVs) in DU145 prostate cancer cells. MVs isolated from UV-treated DU145 and A431 epidermoid carcinoma cells as well as etoposide-treated DU145 cells induced phosphorylation of ataxia-telangiectasia mutated (ATM) at serine 1981 (indicative of ATM activation) and phosphorylation of histone H2AX at serine 139 (γH2AX) in naïve DU145 cells. Importantly, neutralization of MVs derived from UV-treated cells with annexin V significantly reduced the MV-associated BE activities. Etoposide and UV are known to induce DDR primarily through the ATM and ATM- and Rad3-related (ATR) pathways, respectively. In this regard, MV is likely a common source for the DNA damage-induced bystander effect. However, pre-treatment of DU145 naïve cells with an ATM (KU55933) inhibitor does not affect the BE elicited by MVs isolated from etoposide-treated cells, indicating that the BE is induced upstream of ATM actions. Taken together, we provide evidence supporting that MVs are a source of the DNA damage-induced bystander effect.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms18040788