2) Dr. Yanagisawa: How Vitamin C Repairs DNA Damage
Transcription
2) Dr. Yanagisawa: How Vitamin C Repairs DNA Damage
Effect of Vitamin C and antioxidative nutrition on radiationinduced gene expression in Fukushima nuclear plant workers Atsuo Yanagisawa, M.D., Ph.D. Japanese College of IV Therapy 1 !&#$% !"#$% There are many scientific studies demonstrate protective effects of Vitamin C upon radiation-induced cellular injury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amamoto et al. U-B-B020%,2%-+8%7%V-43-2%V,;%"#5#WX5J5SXT5XY8 Fig. 1. Mouse survival after whole body radiation (A). Mice were irradiated at 6, 8, 10, 12, and 14 Gy. The effect of boneM0);,%*0)+4%;).@3@,%+,;;%2<-(%2<-(%&%GF%1<0+,%A04F%3..-43-:0(% marrow transplantation on mouse survival after radiation (B). Mice were irradiated at 10, 12, NOPHQ8%P0(,%B-..01%2.-(;/+-(2-:0(%NPMRQ%"S%<%-D,.%3..-43-:0(% and 14 Gy. Mice received BMT 24 h after radiation. N = 12 in each group. *P < 0.01 vs. other groups. .,;*),4%B3*,%.,*,3@3(>%+,;;%2<-(%5"%GF8%E01,@,.C%(0%B3*,%.,*,3@3(>% 5S%GFTOPH%;).@3@,4C%A,*-);,%0?%.-43-:0(T3(4)*,4%GH%;F(4.0B,8 Prevention of Radiation GI Syndrome by Ascorbic Acid Fig. 3. The K32-B3(%L%FEGD10&H%&H+#>I11-;%0.-++F%-4B3(3;2,.,4%?0.%Z%4-F;C% effect of treatment with ascorbic acid on mouse survival after radiation. The mice were irradiated at 14 Gy -(4%2<,(%2<,%B3*,%)(4,.1,(2%5S%GF%3..-43-:0(8%9.,2.,-2B,(2% and received BMT 24 h after radiation. They received ascorbic acid p.o. for 3 days either before or after radiation, or received distilled water only before radiation. The mice pretreated with ascorbic acid 132<%-;*0.A3*%-*34%B-.[,4+F%3B/.0@,4%.-43-:0(T3(4)*,4% were also irradiated at 14 Gy without BMT. N = 12 in each group, *P < 0.01 vs other groups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f.-+%3(2-[,%0?%@32-B3(%L%/.,@,(2%.-43-:0(T% %%%%%%%3(4)*,4%ab'%4-B->,%3(%<)B-(;8% ]^.$/1(A1+3./1#*+183/#03*1S1(*1OM516/'#*+1 7'.#%#&.13*1A'.64:>N36(:#/.+14)0#*1243/.1 7:((+1$.::6B1 ;'..*1?_91./1#:B1?)/#<(*[email protected].#'$41KE[FEWWYIWENEDC P+004%;-B/+,;%1,.,%2-[,(%A,?0.,%-(4%5%<%-D,.%A.,-[?-;2% 132<%0.-+%3(>,;:0(%0?%@32-B3(%L%NZX%B>_[>Q8%% `-B/+,;%1,.,%3BB,43-2,+F%3..-43-2,4%);3(>%-%L0A-+2TY#% <02;/02%-(4%ab'%4-B->,%1-;%B,-;).,4%);3(>%2<,%c*0B,2c% -;;-F8%% K32-B3(%L%3(>,;:0(%;<01,4%-%;3>(3d*-(2%.,4)*:0(%3(%ab'% 4-B->,%4),%20%3..-43-:0(%-(4%32;%/,-[%,e,*2%1-;%S%<0).% -D,.%3(2-[,%0?%@32-B3(%L8%% V-43-:0(%3(]).F%*-(%A,%/.02,*2,4%% AF%-(:T0=34-:@,%()2.3:0(;%% • f.-+%3(2-[,%0?%-+/<-T+3/03*%-*34%-(4%@32-B3(%g% .,4)*,4%).3(-.F%.-430-*:@32F%-(4%0=34-:@,% ;2.,;;%3(%3..-43-2,4%*<3+4.,(%3(%L<,.(0AF+8% • R<,.,%-.,%()B,.0);%;*3,(:d*%.,/0.2;%-A0)2% ()2.3:0(%-;%-%.-430T/.02,*20.%;)*<%-;%K32-B3(%'C% LC%gC%hC%%`,+,(3)BC%G+)2-2<30(,C%M,+-20(3(C% /.0A30:*;C%V,;@,.-2.0+C%,2*8% • '(:T0=34-:@,%.,;,.@,%0?%2<,%A04F%3;%-%[,F%.0+,% ?0.%/.,@,(:(>%.-43-:0(%3(]).F8% fi*3-+%`2-2,2B,(2%0?%7LHR%-A0)2%% \g(@3.0(B,(2-+%.-430-*:@32F%-(4%<,-+2<^%% %3;;),4%3(%M-.*<%"6C%"#558% `('%3*&1;'()T1(A1R4.1=/#/.0.*/1 5/6)(1a#*#&36#2#1?BOB 1 1?#6#6431b2#7)L1?BOB1 ")'/(*1]B1")'%6(*L1?BOB11 1"'#+A('+1=B1`..%6L1?BOB11 @(*#:+1_)**3*&4#%.L1?BOB1 1=/.8.*1_3$%.>L1-4BOB1 R4(0#619.8>L1?BOB1 It is our strongest recommendation that those living in the effected areas regularly take antioxidant supplements such as vitamin C to counteract the negative consequences of longterm low dose radiation exposure as well as to protect the health of coming generations. a.8%V0(%E)((3(><-[,%%%%%% a.8%`2,@,%E3*[,F a.8%'2;)0%U-(->3;-1- a.8%R<0B-;%g8%j,@F%%%%%%%a.8%P).20(%M8%P,.[;0(%%%a.8%P.-4?0.4%`8%O,,[;%%a.8M-;-;<3%k1-A) 7LHR%T%V,*0BB,(4-:0(% -.(T:.124(14#8.1#1T(6637:.13*/.'*#:1#*+H('1 .c/.'*#:1'#+3#<(*1.cT(6)'.164():+1/#%.1#*<N (c3+#<8.16)TT:.0.*/61/(10#3*/#3*1(T<0#:1#*<N (c3+#<8.1'.6.'8.1(*1/4.3'1(2*17(+>B1 %%K32-B3(%L% % % % %%%%5TZ>%% % %ZTS%:B,;%-%4-F% %%0.%j3/0;0B-+%K32-B3(%L%5T"%>% % % %213*,%-%4-F% %%'+/<-T+3/03*%-*34 % %%%%5##TZ##%B> %213*,%-%4-F% %%`,+,(3)B% % % % %%%%%%X#T"##l> % %213*,%-%4-F% %%K32-B3(%g % % % %%%%5##T"##%B>% %213*,%-%4-F% %%132<%02<,.%,;;,(:-+%@32-B3(;%-(4%B3(,.-+;8% 7LHR%.,*0BB,(4-:0(%?0.%/,0/+,%1<0%10.[;%-2% .-43-:0(T*0(2-B3(-2,4%-.,-%3(%2<,%n)[3;<3B-%% b)*+,-.%9+-(28% N5Q%K32-B3(%L%"X>%38@8%A,?0.,%10.[3(>%-2%()*+,-.%/+-(28% %%%%%%.-43-:0(T*0(2-B3(-2,4%-.,-8%% %%%%%%%%`2,.3+,%1-2,.%%%% % %"X#Bj%% % %X#$%@32-B3(%L%%% %X#Bj% %%%%%%%%"#$%M>T*<+0.34,% %%%%%%XBj %%%%%%%%%%%5$%P5"% % %%%5Bj% %%%%%%%%PT*0B/+,=%5##%%% %%%%%%%%%%%%%%5Bj %%%%%%%%%5#$%PY%%% % %%%5Bj% %%%%%%%%"X$a,=/-(2<,(0+ %%%%%%5Bj% N"Q%a-3+F%;)//+,B,(2;%-2%10.[% %%j3/0;0B-+%K32-B3(%L% %%"%>%m % %2<.,,%:B,;%-%4-F% %%'+/<-T+3/03*%-*34% %%`,+,(3)B% % % %%K32-B3(%g% % % %Z##%B>%m % %213*,%-%4-F% %"##%l>%%m % %213*,%-%4-F% %"##%B>%m %% %213*,%-%4-F% %%132<%02<,.%,;;,(:-+%@32-B3(;8% b-B,+,;;% n-*,+,;;%% E,.0,; Japanese College of Intravenous Therapy (JCIT) We are 400 members: 379 physicians 12 dentists 9 veterinarians More than 10 educational seminars every year. IV Vitamin C, IV Lipoic acid, IV Chelation, Myers’ Cocktail, Ukrain, Nutrition therapy, etc. 24 The 1st JCIT Symposium of ” IVC for Cancer Patients” Oct 17, 2010, Tokyo, Japan "#! $%&'!()*+!,-.!/012!3'34'&! 567+758!%9'&!&*:7%;<&%('5=>'! 3':75*6!5%+8?6(*=%+!(%!! ()'!/*<*+'8'!57=@'+!*6%+A!! ()'!/012!8(*('3'+(B!!! 26 Effect of Vitamin C and antioxidative nutrition on radiationinduced gene expression in Fukushima nuclear plant workers - A pilot study Atsuo YANAGISAWA, M.D., Ph.D. (1) Michie IWATA, M.D., Ph.D. (2) Shuichi AKIYAMA (3) (1) Japanese College of IV Therapy (2) Iwata Ladies Clinic, (3) Gene Science Co, Ltd. 27 H(2.04)*:0(% In the statement of Environmental Radioactivity and Health issued in March 29, 2011, we strongly recommended that People living in the effected areas should regularly take antioxidant supplements such as vitamin C to counteract the negative consequences of long-term low dose radiation exposure as well as to protect the health of coming generations. However, TEPCO, government and all medias ignored our statement. Recently, we examined cancer-related gene expression in 16 men who had worked at severe radiation environment at Fukushima nuclear plant. We also confirmed the improvement of cancer risk score by the supplementation of Vitamin C and other anti-oxidative nutrition. 28 M,2<04;%N5Q%%`2)4F%;)A],*2;% `)A],*2;J% 5Y%B,(%NZ"TX6%F.;8Q%1<0%10.[,4%XTY%1,,[;%-2% .-43-:0(%*0(2-B3(-2,4%-.,-%0?%n)[);<3B-%b)*+,-.% 9+-(2%-D,.%M-.*<%5"C%"#558% '++%;)A],*2;%1,.,%2,B/0.-.F%10.[,.%0?%;)AT;)A% *0(2.-*20.%*0B/-(F%0?%Rg9Lf8% O0.[%0/,.-:0(;%-2%*0(2-B3(-2,4%-.,-J% %%TTo%L0++,*:(>%*0(2-B3(-2,4%1-2,.% %%TTo%M,-;).3(>%.-43-:0(%+,@,+%3(%2<,%/+-(2%-.,-% %%TTo%V,B0@-+%0?%4,A.3;% %%TTo%f/,.-:0(%0?%<,-@F%B-*<3(,.F% 29 M,2<04;%N"Q%%%M,-;).,B,(2% P+004%;-B/+,%1-;%0A2-3(,4%?,1%4-F;%-D,.%2<,% 10.[3(>%/,.3048%H(%S%10.[,.;C%A+004%1-;%0A2-3(,4% -2%A,?0.,%-(4%-D,.%2<,%10.[3(>%/,.3048%%% M,-;).,B,(2J% N5Q%O<0+,%A+004%*0)(2;%-(4%A+004%*<,B3;2.F% N"Q%9+-;B-%+,@,+;%0?%?.,,%ab'% NZQ%Sp%*-(*,.%.,+-2,4%>,(,%,=/.,;;30(% NSQ%L-+*)+-2,%\L-(*,.%V3;[%`*0.,^% \L-(*,.%V3;[%`*0.,^%1-;%*-+*)+-2,4%);3(>%,q)-:0(% ?0.B,4%AF%2<,%+0>3;:*%-(-+F;3;%?.0B%2<,%@-+),%0?% Sp%*-(*,.T.,+-2,4%>,(,%,=/.,;;30(;8% 30 M,2<04;%NZQ%%%%%H(2,.@,(:0(% N5Q H(2.-@,(0);%K32-B3(%L%"X>%/.,;*.3/:0(%% %`2,.3+,%1-2,.%%%% %"X#Bj%%%%%%%%%%%%%5"8X$%M>`fS %XBj %X#$%@32-B3(%L%%% %X#Bj%N"X>Q %% %KTP5J%5"#B> % %KTP"J %%%%%"B>%% %KTPZ%J% %S#B>%% %KTPXJ%%%"XSB>% %KTPYJ% %5"#B>% %KTP5"J%%%%5B>% N"Q%a-3+F%0.-+%;)//+,B,(2;% %% %jF/0;0B-+%K32-B3(%L%%%5%>% % % %'+/<-T+3/03*%-*34 % %Z##%B>% % %`,+,(3)B% % % % %"##%l>%% %% %K32-B3(%g % % % %"##%B>% %M)+:TK32-B3(; % % % % % % % %% % %% %213*,%-%4-F% %213*,%-%4-F% %213*,%-%4-F% %213*,%-%4-F% %213*,%-%4-F% 31 Free DNA concentration (ng/mL plasma) Free DNA Concentration 200 175 Cut-off value <25ng/mL 150 >25ng/mL Healthy control 17% (n=400) Cancer patients 38% (n=400) 125 100 75 50 25 0 32 a3;2.3A):0(%0?%L-(*,.%V3;[%`*0.,%0(%% E,-+2<F%;)A],*2;%-(4%L-(*,.%9-:,(2;8 "#25 !J ■)'*6()H!8?4I'5(8 健常者 ".20 ! ■5*+5'&!<*='+(8 担がん患者 割 合 15 ! 咁 % 咂 ,# 10 ,.! !#! 5 0 !. ∼10 ∼20 ∼30 ∼40 ∼50 ∼60 ∼70 リスク判定値(0∼100) 0*+5'&!C78D!E5%&'!F.;,..G ∼80 ∼90 ∼100 33 9+-;B-%n.,,%ab'%-(4%L-(*,.%V3;[%`*0.,%% 3(%n)[);<3B-%O0.[,.;% ▲ Plasma Free DNA Cancer Risk Score ng/mL ■ ■ "#! !. M! ● KL! !. Cancer Risk Score is calculated from the value of 48 cancerrelated gene expression using logistic analysis. 34 ge,*2%0?%-(:T0=34-:@,%()2.3:0(-+%3(2,.@,(:0(%0(%n.,,% ab'%-(4%L-(*,.%V3;[%`*0.,%3(%n)[);<3B-%O0.[,.;8%% Cancer Risk Score ng/mL FreeDNA "#! KL! !. !. Before 2M NO.B.# Before 2M Five workers were treated with IVC twice a month and oral anti-oxidative nutritional supplements. 35 ge,*2%0?%-(:T0=34-:@,%()2.3:0(%0(%n.,,%ab'%-(4%% L-(*,.%V3;[%`*0.,%A,?0.,%-(4%-D,.%XTY%1,,[;%0?%% ()*+,-.%/+-(2%10.[%-2%n)[);<3B-8% ng/mL Cancer Risk Score FreeDNA KL! "#! !. !. Before After work Before After work Four workers took once i.v. Vitamin C (25g) therapy at before they went, and continuously took anti-oxidative supplements during the working period. No significant change was seen in both Free DNA and Cancer Risk Score. 36 L0(*+);30(% (1) We evaluated the effects of radiation exposure on cancer related gene expression in 17 men who worked 5-6 weeks at the radiation contaminated area of Fukushima nuclear plant. (2) After working, plasma free DNA was increased in 2 of 13 workers, and cancer risk score was increased in 3. After the 2 months intervention with intravenous Vitamin C and oral anti-oxidative nutritional supplements, free DNA returned to normal level and cancer risk score was significantly decreased (p<0.05). (3) No significant change was seen in 4 workers who took once i.v. Vitamin C at before working and continuous intake of anti-oxidative supplements during the working period. (4) Increase in cancer risk by radiation exposure can be protected by anti-oxidative nutritional intervention. Fukushima workers in the radiation contaminated area should take anti-oxidative nutrition therapy immediately. 37 \f(+F%K32-B3(%L%-(4%02<,.%-(:T0=34-:@,%% ()2.3:0);%;)//+,B,(2;%*-(%;-@,%2<,% /,0/+,r;%+3?,%?.0B%.-43-:0(%3(]).F8^% T%7LHR%10.[3(>%>.0)/% 54 yrs. female, stomach cancer 3 yrs after IVC (58 yrs) BW= 40 kg MF%9.0/0;-+% M-3(2-3(3(>%0/:B-+%-(:T0=34-:0(%.,;,.@,%AF% 2-[3(>%K32-B3(%L%-(4%02<,.%-(:T0=34-:@,% ()2.3:0(%3;%,;;,(:-+%?0.%*-(*,.%/.,@,(:0(%-(4% 2.,-2B,(2C%-(2T->3(>C%.-430T/.02,*:0(%-(4% 0/:B)B%<,-+2<8% Thank you ! http://www. iv-therapy.jp P"!