title: Dilution of irradiated cell conditioned medium and the bystander effect.
abstract: While nontargeted and low-dose effects such as the bystander effect are now accepted, the mechanisms underlying the response have yet to be elucidated. It has been shown that the transfer of irradiated cell conditioned medium (ICCM) can kill cells that are not directly irradiated; however, to date the effect of ICCM concentration on cell killing has not been reported. The occurrence of a bystander effect was determined by measuring cell survival after exposure to various ICCM dilutions, using the colony-forming assay, in cells of six human cell lines with varied bystander responses and tumor/ p53 status. Autologous ICCM transfer for these cell lines induced a bystander effect as reported previously. ICCM from these cell lines was transferred to cells of a common reporter cell line (HPV-G) to investigate whether the lack of an induced bystander effect was due to their inability to generate or to respond to a bystander signal(s). ICCM from cells of four cell lines induced a bystander effect in HPV-G reporter cells, confirming that signal production is a critical factor. A saturation response was observed when ICCM was diluted. Survival was found to increase linearly until a plateau was reached and the bystander effect was abolished at 2x dilution. The effect of ICCM from the different cell lines reached a plateau at different dilutions, which were found to correlate with the cell line's radiosensitivity.
authors.affiliation: Medical Physics and Applied Radiation Sciences Department, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: Lorna A
authors.initials: LA
authors.lastname: Ryan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Smith
authors.forename: Colin B
authors.initials: CB
authors.lastname: Seymour
authors.forename: Carmel E
authors.initials: CE
authors.lastname: Mothersill
mesh_terms: D024201:Bystander Effect / Q000502:physiology* / Q000528:radiation effects*; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D017077:Culture Media, Conditioned / Q000378:metabolism* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D011829:Radiation Dosage
chemical_list: D017077:Culture Media, Conditioned