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䠄䠏䠅 ཎᏊ⅔୰ᛶᏊ⥺䛻䜘䛳䛶⏕䛨䜛䠠䠪䠝ᦆയ✀䛾ゎ᫂

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䠄䠏䠅 ཎᏊ⅔୰ᛶᏊ⥺䛻䜘䛳䛶⏕䛨䜛䠠䠪䠝ᦆയ✀䛾ゎ᫂

ᒸᒣ኱Ꮫ⮬↛⏕࿨⛉Ꮫ◊✲ᨭ᥼䝉䞁䝍䞊 ᑎᮾ ᏹ᫂

㏆␥኱ᏛཎᏊຊ◊✲ᡤ ᒣす㻌 ᘯᇛ䚸ᯇ⏣ እᚿᮁ

IIntroduction

㻌 㟁㞳ᨺᑕ⥺䠄௨ୗ䚸ᨺᑕ⥺䠅䛾⏕≀ຠᯝ䛿䚸㑇ఏ≀㉁DNA䛻യᐖ䜢୚䛘䜛䛣䛸䛻䜘䜚⾲ฟ䛩䜛䛜䚸ᨺ ᑕ⥺DNAᦆയ䛻㛵䛩䜛◊✲ᡂᯝ䛿䚸䃒⥺䜔䠴⥺䛺䛹䚸ᚑ᮶䜘䜚ከ⏝䛥䜜䜛⥺✀䛻䜘䜛䜒䛾䛜䜋䛸䜣䛹 䛷䛒䜚䚸䛭䜜௨እ䛾⥺㉁䛻䜘䜛ᦆയ䛾ᵝែ䛿୙᫂䛺Ⅼ䛜ከ䛟ṧ䛥䜜䛶䛔䜛䚹⚾䛿䚸䛭䛾䜘䛖䛺≧ἣ䜢ᡴ

◚䛩䜉䛟䚸㔜⢏Ꮚ⥺䛻䜘䛳䛶⏕䛨䜛DNAᦆയ䛾ศᯒ䜢⾜䛳䛶䛝䛯䠷1, 2䠹䚹䛭䛾◊✲ᡂᯝ䛸䛧䛶䚸㔜⢏

Ꮚ⥺䛾䜘䛖䛺㧗LETᨺᑕ⥺䛷䛿䚸䃒⥺䛾䜘䛖䛺పLETᨺᑕ⥺䛸␗䛺䜛DNAᦆയ✀䛜⏕䛨䜛䛣䛸䚸䜎䛯 䛭䛾཰⋡䛜␗䛺䜛䛣䛸䛜䜟䛛䛳䛯䚹㧗LETᨺᑕ⥺䛻≉ᚩⓗ䛺DNAᦆയᙧែ䛿䜽䝻䝇䝸䞁䜽DNAᦆയ䛸 䜽䝷䝇䝍䞊DNAᦆയ䛾2✀㢮䛜䛒䜛䛜䚸䜽䝻䝇䝸䞁䜽DNAᦆയ䛿䚸䝍䞁䝟䜽㉁➼䛾ศᏊ䛜DNA䛸⤖ྜ䛩 䜛䜒䛾䛷䚸䛭䛾ᔞ㧗䛥䛛䜙DNAྜᡂ㜼ᐖ⬟䛜㧗䛟䚸䜎䛯ಟ᚟ຠ⋡䜒ప䛔䚹୍᪉䚸䜽䝷䝇䝍䞊DNAᦆയ 䛿䚸ᨺᑕ⥺䛜䝡䞊䝮䛸䛧䛶ᶆⓗDNA䜢㏻㐣䛩䜛㝿䛻䚸䛭䛾㌶㊧䛻ἢ䛳䛶」ᩘ䛾ᦆയ䜢⏕䛨䜛䜒䛾䛷䛒 䜛䚹䛣䜜䛿ಟ᚟䝥䝻䝉䝇䛻䜘䜚DNAྜᡂ㜼ᐖ⬟䛜㧗䛟䚸䜎䛯ṇ☜䛺ಟ᚟䛜䛥䜜䛻䛟䛔DNA஧ᮏ㙐ษ᩿

䠄DSB䠅䜢⏕䛨䚸ᨺᑕ⥺⏕≀ຠᯝ䛾୺せᅉ䛸䛥䜜䜛䜒䛾䛷䛒䜛䚹䜽䝷䝇䝍䞊DNAᦆയ䛿䚸ᨺᑕ⥺䛾LET 䛜㧗䛟䛺䜛䜋䛹䚸ᦆയ䛾ᐦ㞟ᗘ䛜㧗䛟䛺䜚䚸⏕≀ຠᯝ䜒኱䛝䛟䛺䜛䚹ཎᏊ⅔୰ᛶᏊ䛿䚸㧗LETᨺᑕ⥺䛷 䛒䜚䚸㔜⢏Ꮚ⥺䛸ྠᵝ䛻䛣䜜䜙2✀㢮䛾DNAᦆയ䛜㧗ຠ⋡䛷⏕ᡂ䛩䜛䛸⪃䛘䜙䜜䚸䛭䜜䛜୰ᛶᏊ⥺≉

␗ⓗ䛺⏕≀ᙳ㡪⾲ฟ䛻㛵䜟䛳䛶䛔䜛䛣䛸䛜ᮇᚅ䛥䜜䜛䚹䛭䛣䛷䚸ᮏ◊✲䛿䚸ཎᏊ⅔୰ᛶᏊ䛻䜘䛳䛶⏕

䛨䜛DNAᦆയ䛾ศᯒ䜢⾜䛔䚸୰ᛶᏊ⥺䛻䜘䜛⏕≀ຠᯝ䛾ศᏊᶵᵓ䛾ゎ᫂䜢┠ⓗ䛸䛩䜛䚹

㻌 䛣䜜䜎䛷䛾◊✲䛷䚸⢭〇䝥䝷䝇䝭䝗DNAศᏊ䜢↷ᑕᑐ㇟䛸䛧䛶ᦆയศᯒ䜢⾜䛔䚸⥺㔞䛻ᛂ䛨䛶୍ᮏ 㙐ษ᩿䠄SSB䠅䛾⏕ᡂ཰㔞䛜ቑ䛘䜛䛣䛸䚸䛭䛾཰㔞䛿0.9 Gy䛷21%䛷䛒䜚䚸䃒⥺䜔䠴⥺䛾཰㔞䜘䜚኱䛝 䛟䚸㔜⢏Ꮚ⥺䛾཰㔞䛻㢮ఝ䛧䛶䛔䜛䛣䛸䛜䜟䛛䛳䛯䚹䛣䛾䛣䛸䛿୰ᛶᏊ⥺䛜㧗LETᨺᑕ⥺䛻≉ᚩⓗ䛺 DNAᦆയ⏕ᡂ䜢♧䛩䛣䛸䜢ព࿡䛩䜛䚹୍᪉䚸ሷᇶᦆയ䜔DSB䛾཰㔞䛿ప䛟䚸㔜⢏Ꮚ⥺䛸␗䛺䜛≉ᚩ 䜢♧䛩䛣䛸䛜䜟䛛䛳䛯䚹

M

Materials and Methods

㻌 ๓㏙䛾㏻䜚䚸⢭〇DNA ศᏊ䜢↷ᑕᑐ㇟䛸䛧䛯ศᯒ䛻䜘䜚䚸୰ᛶᏊ⥺䛾DNA ᦆയ཰⋡䛾ഴྥ䛜ศ 䛛䛳䛯䛣䛸䛛䜙䚸௒ᖺᗘ䛿⣽⬊ෆDNAᦆയ䛾⏕ᡂ䛻䛴䛔䛶᳨ウ䜢⾜䛖䛣䛸䛸䛧䛯䚹䝏䝱䜲䝙䞊䝈䝝䝮䝇 䝍䞊༸ẕ⣽⬊䠄CHO䠅AA8ᰴ䜢ᇵ㣴䛧䚸80%䝁䞁䝣䝹䜶䞁䝖䛻䛺䛳䛯≧ែ䛷䝖䝸䝥䝅䝘䜲䝈ฎ⌮䛻䜘䜚⣽

⬊䜢ᅇ཰䛧䚸25 cm2䝣䝷䝇䝁䛻104ಶ䛪䛴᧛✀䛧䚸1᪥ᇵ㣴䛩䜛䚹䛭䛾ᚋ䚸䝖䝸䝥䝅䝘䜲䝈䛷䝬䜲䜽䝻䝏 䝳䞊䝤䛻⣽⬊䝨䝺䝑䝖≧ែ䛷ᅇ཰䛧䚸㏆␥኱ᏛཎᏊ⅔䛻䛶୰ᛶᏊ⥺↷ᑕ䜢⾜䛳䛯䚹↷ᑕ⥺㔞䛿0䚸0.3䚸 0.6䚸0.9 Gy 䛸䛧䛯䚹ྛ⥺㔞䛷䛾↷ᑕᚋ䚸⣽⬊䜢ᇵᆅ䛻෌ᠱ⃮䛧䚸60 mm䃥䝅䝱䞊䝺䛻෌᧛✀䛧䚸10

᪥㛫ᇵ㣴䛧䚸䝁䝻䝙䞊ᙧᡂ䜢䛥䛫䛯䚹䛭䛾ᚋ䚸䜶䝍䝜䞊䝹ᅛᐃ䜢⾜䛔䚸0.05%䝯䝏䝺䞁䝤䝹䞊䛷ᰁⰍ䛧䚸 䝁䝻䝙䞊䜢ィᩘ䛧䛶䚸⏕Ꮡ⋡䜢⟬ฟ䛧䛯䚹

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― 119 ― R

Results

㻌 ୰ᛶᏊ⥺䛻ᑐ䛩䜛⣽⬊䛾ឤཷᛶ䛿䚸⥺㔞౫Ꮡⓗ䛻ୖ᪼䛧䛯䠄ᅗ䠍䠅䚹䛭䛾ឤཷᛶ䛾ୖ᪼䛿⥺㔞䛻ᑐ 䛧⥺ᙧ䛷䛒䜚䚸୍⯡ⓗ䛺ᨺᑕ⥺ឤཷᛶ䛸ྠᵝ䛷䛒䛳䛯䚹୍᪉䚸䛭䛾ឤཷᛶ䛾ᗘྜ䛔䛿䃒⥺䜔䜶䝑䜽䝇

⥺䛻ᑐ䛧䛶኱䛝䛟䚸D37䛿0.35 Gy䛷䛒䛳䛯䚹䛣䜜䛿䃒⥺䛷䜏䜙䜜䜛್䛾1/10䛷䛒䜚䚸୰ᛶᏊ⥺䛜௚䛾㧗 LETᨺᑕ⥺䛸ྠᵝ䚸㧗䛔⏕≀ᙳ㡪䜢♧䛩䛣䛸䛸୍⮴䛩䜛䚹䜎䛯䚸๓ᖺᗘ䛾⤖ᯝ䛷ᚓ䜙䜜䛯୰ᛶᏊ⥺䛷 䛾㧗䛔DNAᦆയ཰⋡䛸䜒ᩚྜᛶ䛜䛒䜛䚹୍᪉䛷䚸๓ᖺᗘ䛾⤖ᯝ䛷䛿䚸௚䛾㧗LETᨺᑕ⥺䛸␗䛺䜚䚸⣽

⬊䛾⏕Ṛ䛻┤᥋㛵䜟䜛䛸⪃䛘䜙䜜䜛DSB䛾཰㔞䛜ప䛛䛳䛯䛣䛸䛛䜙䚸୰ᛶᏊ⥺䛻ᑐ䛩䜛㧗ឤཷᛶ䛻 㛵䜟䜛DNAᦆയ✀䛾ゎ᫂䛜ᚲせ䛷䛒䜛䚹

F

Future Work

㻌 ௒ᚋ䛿䚸ᇵ㣴⣽⬊䜢⏝䛔䛯⣽⬊ෆDNAᦆയ⏕ᡂ䛾ศᯒ䜢⾜䛔䚸୰ᛶᏊDNAᦆയ䛸䛭䛾⏕≀ᙳ㡪 䛾඲ㇺ䜢᫂䜙䛛䛻䛧䛶䛔䛟䚹

R

References

[1] H. Terato et al., J. Radiat. Res., 49 (2008) 133-146.

[2] Y. Tokuyama et al., J. Radiat. Res., 56 (2015) 446-455.

ᴗ⦼୍ぴ

ᑎᮾᏹ᫂䠈☾㎶䜏䛹䜚䠈ⰼᡣ┤ᚿ䠈ᚫᒣ⏤ె䠈᳃ຍዉᜨ䠈㰺⸨๛䠈ᯇ⏣እᚿᮁ䠈ᒣすᘯᇛ䛂ཎᏊ⅔୰

ᛶᏊ䛻䜘䛳䛶⏕䛨䜛 DNA ᦆയ䛸䛭䛾⏕≀ᙳ㡪䛃᪥ᮏᨺᑕ⥺ᙳ㡪Ꮫ఍➨ 62 ᅇ኱఍䠈2019 ᖺ 11 ᭶ 14-16᪥

ᐇ㦂䞉 ᐃ⿵ຓ⪅

☾㎶䜏䛹䜚䚸ⰼᡣ┤ᚿ䠄௨ୖ䚸ᒸᒣ኱Ꮫ䠅 ᚫᒣ⏤ె䚸᳃ຍዉᜨ䠄௨ୖ䚸బ㈡኱Ꮫ䠅

㰺⸨๛䠄ி㒔኱Ꮫ䠅 䠄ィ䠑ྡ䠅

ᅗ1. ୰ᛶᏊ⥺↷ᑕ䜢⾜䛳䛯CHO-AA8䛾⏕Ꮡ⋡䝥䝻䝑䝖䚹

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