title: Adaptive response in embryogenesis: IV. Protective and detrimental bystander effects induced by X radiation in cultured limb bud cells of fetal mice.
abstract: The radioadaptive response and the bystander effect represent important phenomena in radiobiology that have an impact on novel biological response mechanisms and risk estimates. Micromass cultures of limb bud cells provide an in vitro cellular maturation system in which the progression of cell proliferation and differentiation parallels that in vivo. This paper presents for the first time evidence for the correlation and interaction in a micromass culture system between the radioadaptive response and the bystander effect. A radioadaptive response was induced in limb bud cells of embryonic day 11 ICR mice. Conditioning irradiation of the embryonic day 11 cells with 0.3 Gy resulted in a significant protective effect against the occurrence of apoptosis, inhibition of cell proliferation, and differentiation induced by a challenging dose of 5 Gy given the next day. Both protective and detrimental bystander effects were observed; namely, irradiating 50% of the embryonic day 11 cells with 0.3 Gy led to a successful induction of the protective effect, and irradiating 70% of the embryonic day 12 cells with 5 Gy produced a detrimental effect comparable to that seen when all the cells were irradiated. Further, the bystander effect was markedly decreased by pretreatment of the cells with an inhibitor to block the gap junction-mediated intercellular communication. These results indicate that the bystander effect plays an important role in both the induction of a protective effect by the conditioning dose and the detrimental effect of the challenge irradiation. Gap junction-mediated intercellular communication was suggested to be involved in the induction of the bystander effect.
authors.affiliation: Radiation Hazards Research Group, Radiation Safety Research Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan. jp2813km@nirs.go.jp
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Harumi
authors.initials: H
authors.lastname: Ohyama
authors.forename: Yi
authors.initials: Y
authors.lastname: Shang
authors.forename: Kazuko
authors.initials: K
authors.lastname: Fujita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakajima
authors.forename: Shiro
authors.initials: S
authors.lastname: Aizawa
authors.forename: Osami
authors.initials: O
authors.lastname: Yukawa
authors.forename: Isamu
authors.initials: I
authors.lastname: Hayata
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D024201:Bystander Effect / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D001556:Hexachlorocyclohexane / Q000494:pharmacology; D018878:Limb Buds / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D008813:Mice, Inbred ICR; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D014965:X-Rays
chemical_list: D001556:Hexachlorocyclohexane