title: Bystander effects may modulate ultraviolet A and B radiation-induced delayed mutagenesis.
abstract: Ultraviolet irradiation of cells can induce a state of genomic instability that can persist for several cell generations after irradiation. However, questions regarding the time course of formation, relative abundance for different types of ultraviolet radiation, and mechanism of induction of delayed mutations remain to be answered. In this paper, we have tried to address these questions using the hypoxanthine phosphoribosyl transferase (HPRT) mutation assay in V79 Chinese hamster cells irradiated with ultraviolet A or B radiation. Delayed HPRT(-) mutations, which are indications of genomic instability, were detected by incubating the cells in medium containing aminopterin, selectively killing HPRT(-) mutants, and then treating the cells with medium containing 6-thioguanine, which selectively killed non-mutant cells. Remarkably, the delayed mutation frequencies found here were much higher than reported previously using a cloning method. Cloning of cells immediately after irradiation prevents contact between individual cell clones. In contrast, with the present method, the cells are in contact and are mixed several times during the experiment. Thus the higher delayed mutation frequency measured by the present method may be explained by a bystander effect. This hypothesis is supported by an experiment with an inhibitor of gap junctional intercellular communication, which reduced the delayed mutation frequency. In conclusion, the results suggest that a bystander effect is involved in ultraviolet-radiation-induced genomic instability and that it may be mediated in part by gap junctional intercellular communication.
authors.affiliation: Department of Radiation Biology, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. jostein.dahle@labmed.uio.no
authors.forename: Jostein
authors.initials: J
authors.lastname: Dahle
authors.forename: Olav
authors.initials: O
authors.lastname: Kaalhus
authors.forename: Trond
authors.initials: T
authors.lastname: Stokke
authors.forename: Egil
authors.initials: E
authors.lastname: Kvam
mesh_terms: D000630:Aminopterin / Q000378:metabolism; D000818:Animals; D024201:Bystander Effect; D002450:Cell Communication; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D004307:Dose-Response Relationship, Radiation; D017629:Gap Junctions; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008954:Models, Biological; D016296:Mutagenesis; D009154:Mutation; D011831:Radiation Genetics; D013866:Thioguanine / Q000737:chemistry; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine; D000630:Aminopterin