Abstract
Exosome-like vesicles (ELV) are involved in mediating radiation-induced bystander effect (RIBE). Here, we used ELV from control cell conditioned medium (CCCM) and from 4 Gy of X-ray irradiated cell conditioned medium (ICCM), which has been used to culture normal human fibroblast cells to examine the possibility of ELV mediating RIBE signals. We investigated whether ELV from 4 Gy irradiated mouse serum mediate RIBE signals. Induction of DNA damage was observed in cells that were treated with ICCM ELV and ELV from 4 Gy irradiated mouse serum. In addition, we treated CCCM ELV and ICCM ELV with RNases, DNases, and proteinases to determine which component of ELV is responsible for RIBE. Induction of DNA damage by ICCM ELV was not observed after treatment with DNases. After treatment, DNA damages were not induced in CCCM ELV or ICCM ELV from mitochondria depleted (ρ0) normal human fibroblast cells. Further, we found significant increase in mitochondrial DNA (mtDNA) in ICCM ELV and ELV from 4 Gy irradiated mouse serum. ELV carrying amplified mtDNA (ND1, ND5) induced DNA damage in treated cells. These data suggest that the secretion of mtDNA through exosomes is involved in mediating RIBE signals.
Highlights
The radiation-induced bystander effect (RIBE) was first reported as the phenomenon which involves the induction of sister chromatid exchanges (SCE) by extremely low doses of alpha particles in non-irradiated cells[1]
Since the RIBE was observed in co-culturing systems and medium transfer experiments (Fig. S1), we investigated the possibility of exosome-like vesicles (ELV) being involved in mediating RIBE (Fig. 1A)
We observed significant increase in the frequency of DNA damage foci in cells treated with irradiated cell conditioned medium (ICCM) Exosome-like vesicles (ELV) (1.13 ± 0.31) (p < 0.01) as compared to that in non-treated cells or cells treated with control cell conditioned medium (CCCM) ELV (Fig. 1D,E)
Summary
The radiation-induced bystander effect (RIBE) was first reported as the phenomenon which involves the induction of sister chromatid exchanges (SCE) by extremely low doses of alpha particles in non-irradiated cells[1]. Several evidences suggest that plasma from irradiated animals, including humans, contains factors that are able to cause chromosomal aberrations in non-irradiated cells[17,18,19,20,21,22]. These factors, called clastogenic factors, are very similar effect to RIBE. Lehmann et al reported an increase in the secretion of ELV in the extracellular environment by senescent human prostate cancer cells by clinically relevant doses of irradiation[28]. Our results suggest that mtDNA in ELV are involved in mediating RIBE
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
