Study of effect of ionizing radiation on germline cells

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To investigate positional effects of radiation with an energetic heavy-ion microbeam on germline cells using an experimental model metazoan Caenorhabditis elegans. The germline cells were irradiated with raster-scanned broad beam or collimated microbeam of 220MeV 12C5t particles delivered from the azimuthally varying field (AVF) cyclotron, and subsequently observed for cell cycle arrest and apoptosis. Whole-body irradiation with the broad beam at the L4 larval stage arrested germ cell proliferation. When the tip region of the gonad arm was irradiated locally with the microbeam at the L4 stage, the same arrest was observed. When the microbeams were used to irradiate the pachytene region of the gonad arm, at a young gravid stage, radiation-induced apoptosis occurred in the gonad. In contrast, arrest and apoptosis were not induced in the non-irradiated neighboring region or the opposite gonad. Similar results were confirmed in the c-abl-1 (mammalian ortholog of cellular counterpart of Abelson murine leukemia virus) mutant that is hypersensitive to radiation-induced apoptosis. In addition, we demonstrated that several genes encoding apoptotic cell-death activators and secreted surface proteins were upregulated after ionizing radiation. Some of them were also upregulated by defect of mitochondrial DNA replication. These results indicate that the microbeam irradiation is useful in characterizing tissue-specific, local biological response to radiation in organisms. DNA damage-induced cell cycle arrest and apoptosis were observed in locally irradiated regions, but there was little, if any, ''bystander effect'' in the nematode.