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Cytotoxic Effects of Korean Rice-wine (Yakju) on Cancer Cells

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(1)KOREAN J. FOOD SCI. TECHNOL. Vol. 36, No. 5, pp. 812~817 (2004). ©The Korean Society of Food Science and Technology. z^

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(3) ëW Î BßêÁ~1Ášö'1ÁBêö* ()]B ¦J \², 1^&L ~& >L. Cytotoxic Effects of Korean Rice-wine (Yakju) on Cancer Cells Seung-Jin Kim, Si-Hwan Ko1, Won-Young Lee1, and Gye-Won Kim* Research Laboratories, Kooksoondang Brewery Co., Ltd. Department of Microbiology, School of Medicine, Yonsei University. 1. Cytotoxic effects of Korean rice-wine (Yakju) made with different processes and ingredients (Korean rice-wines I, II), red wine, white wine, beer, and Japanese rice-wine (Sake) were examined against human cancer lines (DLD-1, HepG2, K562) and mouse cancer lines (EMT6, LLC1). Red wine showed cytotoxic effect on all cancer lines, while Korean rice-wines I, and II showed cytotoxcity on all cancer cells except DLD-1. White wine, beer, and Japanese rice-wine had no or little cytotoxic effect against all cancer cell lines. Concentrate of Korean ricewine only showed cytotoxic effect against DLD-1. These results suggest Korean rice-wine has strong anti-cancer effects, which are induced by certain rice-wine components. Key words: cytotoxcity, Korean rice-wine, yakju, anti-cancer, alcohol beverage. B. †. F‚ flavonoid¾ polyphenol~ ·f 'b¾, "~ "öòž jf BÎ"; 7ö WB ôf Wî" jæ" B¢ ŽF ~ ® . ß®, ;‚ “Öz ËKj < ®º jæ" B& ÿ î~ 5 Ëî~~ .Oö êæj "º ©b‚ > ® (2). Ó"~ ãÖöº ŽFB flavonoid¾ polyphenol~ · f 'b¾ öò~ BÎ";öB W>º oligo-peptide& ÷ö W b~ WËÛBf z^ö &‚ “zÎ"¢ ¾æÚº ©b‚ '> ® (12). V¢B rzR rò~ £ÒÎ"º rzR rò~ öòö Ž>Ú ®–¾, $º BÎ"; 7ö WB bî~  çß·Ïö ~š ¢ÚÆ > ®j ©b‚ B΢º ";š Ö 7º† ©b‚ 'B . š‚ &6öB ‚“~ *Û£"ö &šBê š;" &N ~ ôf ºGš ®Úz . ß® ß;‚ ‚£Ò¢ "öò‚ ~ BÎB ãÖöº &æ î÷ö Î"& ®º ©b‚  Î^ "*º»b‚ šÏ>Vê ~& . ¾ *Û£"~  ҂Wö &‚  &æ ³Jö &‚ "'ž 7"š ‡ ‚ ©š * š . Vš ’ 7 Zö BÎ ç"~ jžÖ Žïö &‚ ’(13)f Zö BÎö ~~ B–B 6 £ "~ ³»bš îÖÊ F¾ wï«" žÚ F¾ &Ëz F¾ ^~ WË 5 *š ÛB ‚W(14)j < ®b–, ‚"   ’ê~ ’Ö" *^ Î"¢ {ž~Vê ~& (B‚ – šV). $‚ 6 *Û" 5 " ., ¶ï’î, v~, jš j E, žâ, .EÿÏ~. j '' Î&‚ *Û"öB ACE &š‚W, .*Ϛ‚W, SOD-FÒ ‚W" *¶Ë(“Öz ‚W) ö &‚ ‚;' ’& >Vê ~& (15-22).  ’öBº ‚“~ *Û'ž BÎ O»~ ~¾ž Zö B΢ ۚ ‚£Òf ž öò¢ Î&~ B–B *Û£". ‚" "~ö &‚ ’ 7 ¢ Ó", ê", " ~ B ‚B rÏö ~~ š; 5 î~ö 3;'ž Î"& ®º © b‚ > > ® . rzR Sf Ò†"~ ç&&ê ¢ U $º J; F𢠂*~ ®º–, šº rzRj * & S~æ pº Ò²~ Ò† ';ï~ rzRj S ~º Ò²~ Ò†š Ôjæ "ï~ rzRj S~² > š Ò†š /Ï~² Ã&~º ©j ~‚ (1). š‚ r zR rò~ ';ï Sº Ëî~ ÛB, ÿ ãz jz,  .{, &ê, , zFB ÛB ~ Î"& ®º ©b‚   > ®b–(1-9), ß® ÚÆ‚ rzR ròê ';ïj S ~&j ãÖ ÿ î~ 5 Ëî~~ .Oö – êæj " º ©b‚ C&r (1,2,10). rzR rò~ £ÒÎ"¢ ¾æÚ º Wª 7 &Ë ôš >Úê ©š flavonoidf polyphenol š . ß®, 'ê"~ ãÖ £ 200 «~ ҂Wj < ®º bîš šÒ~–, š f öÒòž êö šÒ~–¾ B Î";ö W>º ©b‚B quercetin, catechin ~ flavonoid ê bî" nonflavonoid ê~ resveratrol š “Öz‚W, ÿ î~ 5 Ëî~~ .O, “z‚W ~ £Ò‚Wj ¾æÚ º ©b‚ rJ^ ® (11). "~ ãÖöº 'ê" Ž *Corresponding author: Gye-Won Kim, Research Laboratories, Kooksoondang Brewery Co., Ltd., Samsung-dong 110-3, Gangnamgu, Seoul 135-090, Korea Tel: 82-2-513-8506 Fax: 82-2-402-5210 E-mail: [email protected] 812.

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(5) V·. þö ÒÏB ^º žÚF¾ «· ^ž DLD-1(&Ëz), HepG2(*z), K562(òW>W W.z)j ÒÏ~&b–, îÖÊ F¾ «· ^ž EMT6(FOz), LLC1(öz)b‚ Îv ^& v ~"& b v öB F 7ž ^¢ ÒÏ~&. . DLD-1f RPMI 1640 Væ(Giboco BRL, Grand Island, NY, USA)ö 10% fetal bovine serum(FBS, Giboco)f streptomycin (100 µg/mL), penicillin(100 U/mL), sodium bicarbonate(2.0 g/L)¢ Î&‚ VæöB V·~&, K562, EMT6, LLC1f DMEM V æ(Gibco)ö 10% fetal bovine serum(FBS)f streptomycin(100 µg/mL), penicillin(100 U/mL), sodium bicarbonate(3.7 g/L)¢ Î& ‚ Væö V·~&b–, HepG2º MEM Væö 10% FBSf streptomycin(100 µg/mL), penicillin(100 U/mL), sodium bicarbonate (2.2 g/L)j Î&‚ VæöB V·~& . Î ^º 37oC, 5% CO2 ~ãöB V·~& . ^

(6) ëW(Cytotoxicity) /; z^"ö &‚ ò~ ëWÎ"º MTT colorimetric assay O»(23)b‚ þ~& . ^¢ 2Ü105 cells/mL‚ ò Ú 35 mm dishöB ª"‚ ò¢ 10, 20, 40, 80V ê'b‚ ’C ~ ^ö ¾Ò~ 37oC, 5% CO2 incubatoröB 24* ÿ n V· Î ê, MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, Sigma, St. Louis, USA) χ 1 mg/mLj '' Î&~ MTT& š z^~ β·Ïö ~š ~ö> êƒ 4* z V·~& . ''~ þ–f 3B~ dish¢ ÿ ¢ –šb‚ ~ þ~& . V· «ò  öªÒ~ ç [‡j B–~ ~[¦ö DMSO 100 µL¢ Î&š WB formazan Ö;j ϚÊ, 100 µL~ isopropanolj ¾Ò~ >wj 7æB 570 nmöB ‡7ê¢ G;~& . MTT G; »b‚ G;B &––" þ–~ O.D. 8j r" ?š j ¾~ êÖö ~š ^ëWNj ’~& .. 813. " &––~ ^ ηj 7*ã(Carl zeiss, Germany)j š Ï~ &V~&, Vö ËOB šz¢¢ šÏ~ 400VN ‚ Òêj 3Ú jv~& . Ûê¾Ò Î þÖ"~ Ûê¾Òº GraphPad Prism ²*ÞÚ(ª * 3.0)j šÏ~ ^ëWNö &‚ ï8" ‚&ÞN‚ ¾ æÚî .. Ö 5 V ‚“ *Û£"f 6> ®º  rzR ròö ŽF> Ú ®º Wª ~ z^"ö &‚ ^ëWj G;~V *~ , ' «~~ Fj žÚ F¾ ^" DLD-1, HepG2, K562f îÖÊ F¾ ^" EMT6, LLC1ö 10-80V~ ’CV>‚ Î &~ z^~ ښËj MTTO»b‚ jv~& . ^ë Wf jߚ' OÚV*b‚B z^ö ç7'b‚ ¶çj * öò jî¢ ÿb ÚÚ â*’¾ &^f ?š ‚'^ ö &~ ^ëWÎ"¢ ¾æÚº ·ÿ^¢ ¶Žb‚Ž  ^ëWÎ"¢ “êÎ º & ® (24). žÚF¾ ^

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(8) ëW Î žÚ &Ëz F¾ «·^ž DLD-1ö &‚ þÖ"º Fig. 1" ? . 'ê"~ ãÖ 10V ’CV>öB 67.25%, 20V ’CV>öB 72.51%~ ^ëWj ¾æÚº ©b‚ j, V šö  >Úê ©¾" 'ê"º ;‚ ^ëWj ¾æÚ  ®º ©j r > ® . ö jš *Û£"I ~ ãÖ 10V ’CV>öB 24.15%, 20V ’CV>öB 21.47%‚ 'ê" ö jš 3V;ê Ôf ^ëWj &b–, ¢Ó"~ ãÖ öº 10VöBº *Û£"I" F҂ ^ëWj šæò, ’ CV>& Ã&†>ƒ 6²>º ãËj & . Wê"  £ 20%;ê~ ^ëWj 10V ’CV>öB &æò  Î "& ’CV>& Ã&†>ƒ 6²~º ©j {ž~& . " ¾ *Û£"II~ ãÖöº  Î"& 10%òb‚ ^ëW Î "& ~& . 'ê"~ šf ?f ^ëWf resveratrol " ?f polyphenolö ~‚ 'Ëö ~‚ ©b‚ > ®. (25,26). $‚, Ö"‚ B~æ p~æò ¢Ó"f *Û£" Ij 10V 6{ ³»~ DLD-1ö ¾Ò~&j ãÖ *Û£"I öBº Red wine 10V ’CV>f F҂ ^ëWj < ® îb–, ¢Ó"~ ãÖöº Î"& ìº ©j {ž~& . š. Inhibition ratio(%)={(&–– O.D.− þ– O.D.)/&–– O.D.}Ü100 Photomicrography ^~ ;'ž æz¢ &V~V *š ''~ ^ f ò ¾Ò *" ò ¾Ò ê 24* ÿn V·~šB þ–. Fig. 1. Inhibitory effects of each alcohol beverage on the viability of DLD-1 human colon cancer cells in MTT assay..

(9) 814. ‚“®"²æ B 36 ² B 5 ^ (2004). Fig. 2. Inhibitory effects of each alcohol beverage on the viability of HepG2 human hepatocellular carcinoma cells in MTT assay.. Fig. 3. Inhibitory effects of each alcohol beverage on the viability of K562 human leukemia cells in MTT assay.. º ^ëW~ Î"¢ ¾æÚº æ~ Wªš *Û£"Iö  ï šÒ‚ º ©j ¾æÞ . *z^"ž HepG2~ ãÖ 'ê", *Û£"I, IIöB ^ ëWj ¾æÚº ©j {ž† > ®î (Fig. 2). 10V ’C V>öBº 'ê", *Û£"I, II& F҂ ^ëWj & æò, 20V ’CV>öBº 'ê"& 40.98%~ ^ëWj  *Û£"I, II ^ëWš – ©j r > ®b–, * Û£"I~ ãÖ 20V ’CV>öB Î"& –~ ìº ©j { ž ~& . ¾ Ó"¾ ", Wê"öBº ^ëW~ Î "& 10% òb‚ –~ Î"& ìº ©j {ž~& . W.z F¾ K562ö &‚ þÖ"º Fig. 3" ? . *~. þ Ö"f FÒ~² 'ê", *Û£"I, II~ 10V ’CV >öB ^ëWš 'ê" 90.48%, *Û£"I 91.26%, *Û £"II 88.61%‚ Ö ;‚ ^ëWj ¾æÚº ©j {ž~ & . ~æò 20V ’CV>öBº 'ê"& 59.46%, *Û£ "I 34.01%, *Û£"II 54.06%~ ^ëWj  'ê"f *Û£"II& F҂ ^ëWj š, *Û£"Iš ž v ò £‚ ^ëWj ¾æÚº ©j r > ® . K562ö Bê  Ó", " 5 Wê"öB 10% ڞ~ £‚ ^ ëWòš {ž>î . îÖÊ F¾ «· ^

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(11) ëW Î îÖÊ F¾ FOz ^"ž EMT6ö &‚ ^ëWÎ"º Fig. 4ö ¾æÞ :f ?š žÚ F¾ ^"öBf ÿ¢~² 'ê", *Û£"I, IIöBò ;‚ ^ëW𠾿¾º ©j {ž † > ®î . 10V ’CV>öBº 'ê" 90.19%, *. Fig. 4. Inhibitory effects of each alcohol beverage on the viability of EMT6 mouse breast cancer cells in MTT assay.. Fig. 5. Inhibitory effects of each alcohol beverage on the viability of LLC1 mouse lung cancer cells in MTT assay.. Û£"I 90.54%, *Û£"II 88.61%~ ^ëWj  F҂ Î"¢ {ž† > ®î . ~æò 20V ’CV>öBº *Û£ "I 70.15%, *Û£"II 63.24%, 'ê" 40.42%‚ *Û£"I ~ ^ëWš &Ë ;‚ ©j r > ®î . Wê", ¢ Ó", "~ ãÖ ’CV> 10VöB '' 19.42%, 11.70%, 17.30%~ ^ëWj  FOz ^"öB £~æò ^ ëWj < ®º ©j {ž† > ®î . ~æò 20V šê ~ ’CV>öBº  Î"& –~ ìî . öz ^"ž LLC1ö &‚ MTT assayö ~‚ ^ëW. þÖ"º Fig. 5ö ¾æÚî . MTT assay G; Ö"º „~ Ö"f îR&æ‚ 10V ’CB *Û£"I, IIöBò ^ëW š ;~² ¾æÒb–, ߚ~²ê 20V~ ’CV>öBº Î  òöB ^ëWš 10% ڞ‚ <öº ¾æ¾æ p~ . 10V ’C V>öBê *Û£"I" *Û£"IIº 86.77%f 85.83%~ Ö ;‚ ^ëWj &æò 'ê"~ ãÖö º 50.13%‚ 7*;ê~ ^ëWj ¾æÚî . ê³>º. þÖ"f îR&æ‚ Ó"¾ "öBº ^ëWš 10% Ú ž‚ Ô² &V>î . z^

(12) ~ *ã V žÚF¾ &Ëz ^" DLD-1" *z ^" HepG2~ ^  æz¢ ÚÚV *~ *ã &Vj ~& (Fig. 6 5 7). ' 10V ’CV>‚ ’CB rzR rò¢ ¾Ò‚ ê 24* Êö ¾æÂ Ö"¢ ÚÚš DLD-1~ ãÖ 'ê" öBò ^ëWš &V>î, HepG2~ ãÖöº *Û£"I, II, 'ê"öBò ^ëWš &V>î . š‚ Ö"º MTT.

(13) z^ö &‚ ‚“ *Û£"~ ^ëW Î". 815. Fig. 6. Photomicrograph of DLD-1 cell treated which 24 hr cytotoxicity of addition with different alcohol beverages. A: Control, B: Korean rice-wine I, C: Korean rice-wine II, D: Red wine, E: White wine, F: Japanese rice-wine, and G: Beer.. Fig. 7. Photomicrograph of HepG2 cell treated which 24 hr cytotoxicity of addition with different alcohol beverages. A: Control, B: Korean rice-wine I, C: Korean rice-wine II, D: Red wine, E: White wine, F: Japanese rice-wine, and G: Beer.. £j šÏ‚ ^ëW þ" ?f Ö"ªj {ž† > ® î . –šV‚ "æ p~æò Î z^ö &~ ÿ¢ ‚ þj >¯~&b–, Îv MTT assayÖ"f ÿ¢‚ ©j {ž† > ®î .  ’¢ >¯~º ";öB –šV¢ šæ p~æò ' "~& < ®º Ôf pHö ~‚ ^ëW Î"f Ž>Ú ®º , rzR ö ~‚ ^ëW ¦¢ 6;~& . pH~ ãÖöº Î "~öB pH 2-3~ Ôf pH¢ &æ ®îæ ò, ò¢ Îv pH 7.4‚ ;~ê ^ëW~ Î"öº N š& ìîb–, ŽFB rzRö ~‚ ^ëW Î"& ìrj {ž~& . $‚ žÚ F¾ &Ëz ^" DLD-1ö &‚ Ó. " 5 *Û£"I~ ³»‡ þ, "~ö ŽB " ÿ¢‚ ³ê~ j šÏ‚ ^ëW þ  ÚÆ‚ ^ëWj & V† > ìî . Vš ¢ Û~ ‚“ *Û£" Wªš Ú ÚöB z^~ WËj ÛB~º >šö B ^ëWf r J^ ®º ž  “zbî ö jš ç® Ôf ©b‚ >î (14). $‚ ¢ Ó"ö &NB ’ö ~~š z^ ö V¢ 64V šç~ ’CV>öB ^ëWj & º  & ® (12). ¾ ; ~ ’¢ Û~ ¢ Ó"& ’ CV>& 1-8V òöBò Î"& ®î  >î . $‚ ‚“ *Û£"& ¢ç'ž rÏ º* ÚöB ^ö &‚ ç 7'ž ëWš £~&b¾, Ôf ’CV>öBê &ç ^.

(14) ‚“®"²æ B 36 ² B 5 ^ (2004). 816. ~ ; æz¢ Fê~º ©b‚ ~&æò,  þ~ Ö"¢ š ‚“*Û£"I, IIº ^ëW~ Î"& ¾ rJ^ ®º 'ê"f –~ F҂ ^ëWj ¾æÚîb–, ^ ~ ;æz¢ Fê~æ p~ . $‚, Vš öB ^ë Wš rJê Ó", ", Wê"~ ãÖöº ^ëW Î" & £‚ ©j {ž~& . ¢>'b‚ 'ê"~ “«· Î"~ ãÖ 'ê"ö & ïb‚ ŽF>Ú ®º polyphenol(1.8 g/L)ö ~‚ ©b‚  > ® (11). ¶ÚG; Ö" *Û£"I~ ãÖ £ 30-40 mg/ L, *Û£"II~ ãÖ £ 100-120 mg/L‚ 'ê"ö jš ' f ·~ polyphenolj ŽF~ ®, *Û£" ôf ·~ polyphenolj ŽF~ ®º Wê"(200-300 mg/L)& *& ^  ëWj ¾æÚæ á~º ©b‚ {ž>îV r^ö, *Û£ "~ “«· ^ëW~ ãÖ ŽFB polyphenol~ Î" º *Û£"I" IIö ŽFB &æ Wª" BÎ";öB W >º ' òö Û'b‚ ŽFB Wªš “«· Î"¢ F êš Þ ©b‚ ÒòB . š‚ *Û£"& <º £Ò'ž Î"¢ ª«~² «Ã~ V *šBº  Úê'š 7º*‚ þj ۂ ’Ú'ž ¶ò¢ jº‚ ‚ . ê³>º ’¢ ۚ ÖF ‚“ *Û£ "~ Wª j ª³~ „B Þ/‚ Î" ö Î"& ®º W ªj ªC~¢ † ©š . ÿö ^ëWš ÚÆ‚ ·ÏV *ö ~š ¢Ú¾ ®ºæö &‚ ’ê jº~ .  ’ º Všö z^ö &‚ ^ëWš  >î~ rzR r òf *Û£"ö &‚ ^ëWj jv, ¦ÃŽb‚Ž *Û£ "& z^ö &‚ 3;'ž Î"¢ < ® º 7º‚ " –¢ B~ ® .. º. £. ‚“ *Û£"f Všö z^"ö &‚ ^ëWš  >Ú ®º rzR ròö &‚ “«· ^ëWj jv~V * ~ Zö BÎ O»b‚ BÎʚB ‚£Ò¢ Î&‚ * Û£"I" {´, z& j Î&‚ *Û£"II, jv ò‚ ' ê", Wê", ", ¢ Ó" ö &~ ’~& . ' òö &~ 10-80Vræ ê'b‚ ’C~ DLD-1, HepG2, K562, EMT6, LLC1ö ¾Ò~&j r, žÚF¾ &Ë z ^"ž DLD-1~ ãÖ 'ê"öBò ;‚ ^ëWš {ž>, *Û£"I~ ãÖ  ³»‡öB DLD-1ö &~  'ê"f F҂ ^ëWj {ž† > ®î . ¾^æ 4 «~ z^"öBº 10-20V ’CV>öB 'ê", *Û£ "I, *Û£"II& ^ëWj &b¾, ' z^"~ «~ö V¢B ^ëWf £*O Nš¢ & . HepG2, K562, EMT6 ~ ãÖ 10V ’CV>öB Îv j݂ ^ëWj ž > šö îÖÊ F¾ öz^"ž LLC1~ ãÖöº *Û£"I" *Û£"II~ ^ëWš 'ê" Ö>‚ ©j {ž~&. .  ’~ Ö"ö ~~š š‚ “zÎ"º *Û£"ö šÒ~º æ~ £ÒWªš ·Ï~º ©b‚ 6>î .. ^. ò. 1. de Lorimier AA. Alcohol, wine, and health. Am. J. Surg. 180: 357-361 (2000) 2. Denke MA. Nutritional and health benefits of beer. Am. J. Med. Sci. 320: 320-326 (2000) 3. Miyagi Y, Miwa K, Inoue H. Inhibition of human low-density. lipoprotein oxidation by flavonoids in red wine and grape juice. Am. J. Cardiol. 80: 1627-1631 (1997) 4. Pace Asicak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: Implications for protection against coronary heart disease. Clin. Chim. Acta. 235: 207-219 (1995) 5. Hayek T, Fuhrman B, Vaya J, Rosenblat M, Belinky P, Coleman R, Elis A, Aviram M. Reduced progression of atherosclerosis in apoplipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin is associated with reduced susceptibility of LDL to oxidation and aggregation. Arterioscler. Thromb. Vasc. Biol. 17: 2744-2752 (1997) 6. Clifford AJ, Ebeler S, Ebeler JD, Bills ND, Hinrichs SH, Teissedre PL, Waterhouse AL. Delayed tumor onset in transgenic mice fed an amino acid-based diet supplemented with fed an amino acid-based diet supplemented with red wine solids. Am. J. Clin. Nutr. 64: 748-756 (1996) 7. Stoewsand GS, Anderson J, Munson L. Inhibition by wine of tumorigenesis induced by ethyl carbamate (urethane) in mice. Food Chem. Toxicol. 29: 291-295 (1991) 8. Soleas GJ, Diamandis EP, Goldberg DM. Wine as a biological fluid: history, production, and role in disease prevention. J. Clin. Lab. Anal. 11: 287-313 (1997) 9. Arimoto-Kobayashi S, Sugiyama C, Harada N, Takeuchi M, Takemura M, Hayatsu H. Inhibitory effects of beer and other alcoholic beverages on mutagenesis and DNA adduct formation induced by several carcinogens. J. Agric. Food Chem. 47: 221230 (1999) 10. Curtis ER. Balancing the risks and benefits of moderate drinking. Ann. N.Y. Acad. Sci. 975: 1-6 (2002) 11. German JB, Walzem RL. The health benefits of wine. Ann. Rev. Nutr. 20: 561-593 (2000) 12. Takizawa Y, Itou R, Yoshida Y, Kudou K. Effect of Sake extracts on the growth of bacteria and human cell lines. Yuhobika 58: 437-440 (1994) 13. Shon SK, Rho YH, Kim HJ, Bae SM. Takju brewing of uncooked rice starch using Rhizopus koji. Korean J. Appl. Microbiol. Biotech. 18: 506-510 (1990) 14. Chung KS, Oh WT, Nam SM, Son BS, Park YS. Effect of Korean rice-wine (Yakju) on in vitro and in vivo progression of B16BL6 mouse melanoma and HRT18 human colon adenocarcinoma cells. Korean J. Food Sci. Technol. 30: 1470-1475 (1998) 15. Han KH, Lee JC, Lee GS, Kim JH, Lee JS. Manufacture and physiological functionality of Korean traditional liquor by using purple-fleshed sweet potato. Korean J. Food Sci. Technol. 34: 673-677 (2002) 16. Kim JH, Lee DH, Choi SY, Lee JS. Characterization of physiological functionalities in Korean traditional liquors. Korean J. Food Sci. Technol. 34: 118-122 (2002) 17. Kim JH, Jeong SC, Kim NM, Lee JS. Effect of Indian millet koji and legumes on the quality and angioteinsin I-converting enzyme inhibitory activity of Korean traditional rice wine. Korean J. Food Sci. Technol. 35: 733-737 (2003) 18. Kim JH, Lee JH, Kim HJ, Choi SY, Lee JS. Effect of barley koji and legumes on the quality and fibrinolytic activity of Korean traditional rice wine. J. Korean Soc. Food Sci. Nutr. 32: 1066-1070 (2003) 19. Seo SB, Kim JH, Kim NM, Choi SY, Lee JS. Effect of Acasia (Robinia pseudo-acasia) flower on the physiological functionality of Korean traditional rice wine. Korean J. Microbiol. Biotechnol. 30: 410-414 (2002) 20. Kim HJ, Lee JC, Lee GS, Jeon BS, Kim NM, Lee JS. Manufacture and physiological functionalities of traditional ginseng liquor. J. Ginseng Res. 26: 74-78 (2002) 21. Kim JH, Lee SH, Kim NM, Choi SY, Yoo JY, Lee JS. Manufacture and physiological functionality of Korean traditional liquor by using Dandelion (Tarax-acum platycarpum). Korean J. Appl. Microbiol. Biotechnol. 28: 367-371 (2000) 22. Lee DH, Kim JH, Kim NM, Pack JS, Lee JS. Manufacture and physiological functionality of Korean traditional liquors by using Paceilomyces japonica. Korean J. Mycol. 30: 142-146 (2002).

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