• 제목/요약/키워드: phase 1 metabolism

검색결과 140건 처리시간 0.031초

사료 중 미역은 복강내 LPS 주입 육계 병아리에서 영양소 대사, 항산화계 및 면역 반응을 조정한다 (Dietary Brown Seaweed Modulates Nutrient Metabolism, Anti-oxidant System and Immune Response in Broiler Chicks Injected LPS i.p.)

  • 박인경;임진택;최도열;고태송
    • Journal of Animal Science and Technology
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    • 제50권2호
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    • pp.185-198
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    • 2008
  • 급성기 반응 중인 육계 병아리에서 미역 2.0% 사료가 영양소 대사, 항산화 효소활성 및 세포성 면역에 미치는 영향이 조사 되었다. 갓 부화한 숫 육계 병아리(Ross)는 4주간의 실험 사육기간에 미역 0.0%(기초) 및 2.0% 사료를 급여하고, 8, 10, 및 12일령에 Salmonella typhymurium lipopolysaccharide(LPS)를 복강내 주입하여 급성기 반응을 활성화 하였다. 실험사육 전기간을 통한 생산성은 사료 중 미역 함량이나 급성기 반응 또는 그 경험의 영향이 없었다. 대조(정상) 병아리에 비하여, 급성기 반응은 미역 2.0% 사료에서 일당 증체량에 영향이 없었으나, 혈장 과산화물 분해효소, 세포외액 SOD(EcSOD) (p<0.05), 적혈구 MnSOD와 CuZnSOD 활성을 높이고, 그리고 사료 중 미역 함량과 관계없이 대사체중(kg0.75) 당 NB와 ME이용량를 낮추고 TNF-α와 ovotransferrin 활성을 높였다. 미역 0.0% 사료에 비하여, 미역 2.0% 사료는, 급성기 반응과 관계없이 kg0.75 당 NB를 증가시켰고, 급성기 반응 중에는 kg0.75당 UAN 배설에 영향이 없었으나, 혈장 과산화물 농도와 적혈구 세포액의 과산화물 분해효소와 MnSOD(p<0.05) 활성을 낮추고 혈장 과산화물 분해효소와 EcSOD 활성은 높이고(p<0.05), 4주령 병아리에서 LPS 자극 PBMC에서 분비한 IL-1 활성을 증가시켰다.(주 단어:미역, LPS, 단백질과 에너지대사, 항산화계, 친염증성 사이토카인, PBMC, 육계 병아리)

홍국고구마가 고지방식이를 급여한 흰쥐의 배변량 및 지질대사에 미치는 영향 (Effect of Diets with Red Yeast Sweet Potato Powder Supplement on Fecal Amount and Lipid Metabolism in Rats Fed a High-fat Diet)

  • 박주헌;최상윤;이경원;김성수;조경동;한찬규
    • 한국식품영양과학회지
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    • 제41권4호
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    • pp.487-493
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    • 2012
  • 홍국고구마가 고지방식이를 섭취한 흰쥐의 배변량 및 지질대사 개선에 미치는 영향을 조사하고자 SD계 수컷 흰쥐를 대상으로 실험 1기(6주)에 고지방식이를 급여하고, 실험 2기(4주)에 3종의 고구마분말(일반, 홍국, 자색)을 5% 첨가한 식이를 급여했을 때, 배변량은 홍국고구마군(RYSP)이 고지방대조군(CON)에 비해 유의하게 증가하였고(p<0.05), 장 통과시간 역시 RYSP군이 가장 짧았다. 분변 중 총콜레스테롤(TC) 함량은 일반고구마군(WFSP)과 홍국고구마군(RYSP)이 유의하게 높았고(p<0.05), 그중에서도 RYSP군이 더 높은 함량을 나타내었으며, 중성지방(TG) 농도는 RYSP군이 WFSP군과 PFSP(자색고구마)군에 비해 각각 9%, 26% 더 높았으나 유의성은 없었다. 반면 1일 총 지질배설량은 TC와 TG 모두 RYSP군이 CON군과 PFSP군에 비해 유의적으로 높았다(p<0.05). 혈청 중 TC 농도는 RYSP군이 CON군에 비해 유의적 차이 없이 20% 감소하였고, LDL-C 농도는 RYSP, PFSP군이 CON군보다 통계적으로 유의하게 낮았으며(p<0.05), TG 농도는 RYSP군이 실험군중 가장 낮았고 이는 WFSP군과 유의적인 차이가 있었다(p<0.05). 이상의 결과에서 홍국고구마 식이는 배변량을 증가시키고, 분변 중 지질 배설량을 다소 증가시키며, 혈청 지질 농도의 감소 효과를 확인할 수 있었다.

한국인 두경부암종 환자에서 Cytochrome P450 1A1, 2E1 및 N-acetyltransferase 2 효소의 다형성 분석에 따른 유전적 감수성에 대한 연구 (GENETIC SUSCEPTIBILITIES OF CYTOCHROME P450 1A1, 2E1, AND N-ACETYLTRANSFERASE 2 TO THE RISKS FOR KOREAN HEAD AND NECK CANCER PATIENTS)

  • 이영수;김태균;우순섭;심광섭;공구
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제22권4호
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    • pp.373-382
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    • 2000
  • Individual genetic susceptibilities to cancers may result from several factors including differences in xenobiotics metabolism to chemical carcinogens, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. Among them, genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. They have two main types of enzymes: the phase I cytochrome P-450 mediating enzymes (CYPs) and phase II conjugating enzymes. The purpose of this study is to determine the frequencies of genotypes of phase I (CYP1A1 and CYP2E1) and phase II (NAT2) metabolizing enzymes in healthy control and head and neck cancer patients of Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer in Korean. The author has analyzed 132 head and neck cancer patients and 113 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results were as following; 1. The frequencies of genotypes of CYP1A1, CYP2E1 and NAT2 in healthy control were as following; CYP1A1 exon 7 polymorphism; Ile/Ile: Ile/Val: Val/Val = 59.3%: 36.3%: 4.4% CYP2E1 Pst I polymorphism, C1/C1: C1/C2: C2/C2 = 61.1%: 32.1%: 6.2% NAT2 polymorphism; F/F: F/S: S/S = 43.4%: 48.7%: 8.0% 2. In analysis of phase I enzyme, Val/Val genotype in CYP1A1 exon 7 polymorphism and C2/C2 genotype in CYP2E1 Pst I polymorphism were associated with relative high risks to head and neck cancers (Odds' ratio: 2.09 and 1.37, respectively). 3. Among the genotypes of NAT2 enzyme polymorphism, S/S genotype of NAT2 enzyme had 1.03 times of relative risk to head and neck cancers. 4. In combined genotyping of CYP1A1, CYP2E1, and NAT2 enzymes polymorphisms, the patients with Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator had higher relative risks than the patients with each baseline of combined genotypes (Odds' ratio: 2.82, 1.98 and 2.1, respectively). These results suggest the combined genotypes of Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator were more susceptible to head and neck cancers in Korean. And genotyping of metabolizing enzymes could be useful for predicting individual susceptibility to head and neck cancer.

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Muscle oxygenation, endocrine and metabolic regulation during low-intensity endurance exercise with blood flow restriction

  • Hwang, Hyejung;Mizuno, Sahiro;Kasai, Nobukazu;Kojima, Chihiro;Sumi, Daichi;Hayashi, Nanako;Goto, Kazushige
    • 운동영양학회지
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    • 제24권2호
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    • pp.30-37
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    • 2020
  • [Purpose] The present study investigated the effect of endurance exercise with blood flow restriction (BFR) performed at either 25% maximal oxygen uptake (${\dot{V}}O_2$ max) or 40% ${\dot{V}}O_2$ max) on muscle oxygenation, energy metabolism, and endocrine responses. [Methods] Ten males were recruited in the present study. The subjects performed three trials: (1) endurance exercise at 40% ${\dot{V}}O_2$ max without BFR (NBFR40), (2) endurance exercise at 25% ${\dot{V}}O_2$ max with BFR (BFR25), and (3) endurance exercise at 40% ${\dot{V}}O_2$ max with BFR (BFR40). The exercises were performed for 15 min during which the pedaling frequency was set at 70 rpm. In BFR25 and BFR40, 2 min of pressure phase (equivalent to 160 mmHg) followed by 1 min of release phase were repeated five times (5 × 3 min) throughout 15 minutes of exercise. During exercise, muscle oxygenation and concentration of respiratory gases were measured. The blood samples were collected before exercise, immediately after 15 min of exercise, and at 15, 30, and 60 minutes after completion of exercise. [Results] Deoxygenated hemoglobin (deoxy-Hb) level during exercise was significantly higher with BFR25 and BFR40 than that with NBFR40. BFR40 showed significantly higher total-hemoglobin (total-Hb) than NBFR40 during 2 min of pressure phase. Moreover, exercise-induced lactate elevation and pH reduction were significantly augmented in BFR40, with concomitant increase in serum cortisol concentration after exercise. Carbohydrate (CHO) oxidation was significantly higher with BFR40 than that with NBFR40 and BFR25, whereas fat oxidation was lower with BFR40. [Conclusion] Deoxy-Hb and total Hb levels were significantly increased during 15 min of pedaling exercise in BFR25 and BFR40, indicating augmented local hypoxia and blood volume (blood perfusion) in the muscle. Moreover, low-and moderate-intensity exercise with BFR facilitated CHO oxidation.

The Effects of Copper Source and Concentration on Lipid Metabolism in Growing and Finishing Angus Steers

  • Johnson, L.R.;Engle, T.E.
    • Asian-Australasian Journal of Animal Sciences
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    • 제16권8호
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    • pp.1131-1136
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    • 2003
  • Forty-eight individually fed Angus steers (body weight $220kg{\pm}9.1$) were utilized to investigate the effects of copper (Cu) source and concentration on lipid metabolism and carcass quality. Steers were stratified by body weight and initial liver Cu concentration and randomly assigned to one of five groups. Groups were then randomly assigned to treatments. Treatments consisted of: 1) control (no supplemental Cu); 2) 10 mg Cu/kg DM from $CuSO_4$; 3) 10 mg Cu/kg DM from a Cu amino acid complex (Availa Cu) 4) 20 mg Cu/kg DM from $CuSO_4$; and 5) 20 mg Cu/kg DM from Availa Cu. Steers were fed a corn-alfalfa-based growing diet for 56 d. Steers were then switched to a high concentrate finishing diet for 145 d. On day 74 of the finishing phase subcutaneous adipose tissue biopsies were obtained from three steers/treatment to determine basal and stimulated lipolytic rates in vitro. Steers were then slaughtered after receiving the finishing diet for 145 d. Control steers tended (p<0.12) to have lower ceruloplasmin (Cp) activity than Cu supplemented steers. Steers receiving 20 mg Cu/kg DM from Availa Cu had higher (p<0.03) Cp activity than steers receiving 20 mg Cu/kg DM from $CuSO_4$. Plasma non-esterified fatty acids were similar across treatments. Steers receiving 10 mg Cu/kg DM from Availa Cu had higher (p<0.02) total plasma cholesterol concentrations relative to steers receiving 10 mg Cu/kg DM from $CuSO_4$. Steers receiving 20 mg Cu/kg DM from Availa Cu had lower (p<0.03) plasma triglyceride concentrations than steers supplemented with 20 mg Cu/kg DM from $CuSO_4$. Fatty acid profile of longissimus muscle was similar across treatments. Backfat depth tended (p<0.18) to be lower in Cu supplemented steers relative to controls. Steers supplemented with 20 mg Cu/kg DM from Availa Cu had heavier (p<0.03) hot carcass weights and a greater (p<0.02) dressing percentage than steers supplemented with 20 mg Cu/kg DM from $CuSO_4$. Furthermore, in vitro basal (p<0.06) and epinephrine stimulated (p<0.04) lipolytic rates of subcutaneous adipose tissue were higher in Cu supplemented steers relative to controls. The results of this study suggest that Cu supplementation has minimal effects on blood and lean tissue lipid profile. However, it appears that Cu may play a role in lipid metabolism in subcutaneous adipose tissue.

Chiral Separation of the Enantiomers of Metoprolol and Its Metabolites by High Performance Liquid Chromatography

  • Kim, Kyeong-Ho;Shin, Sang-Duk;Lee, Joo-Hyun;Lee, Sang-Cheal;Kang, Jong-Seong;Mar, Woong-chon;Hong, Seon-Pyo;Kim, Hyun-Ju
    • Archives of Pharmacal Research
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    • 제23권3호
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    • pp.230-236
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    • 2000
  • (1'R, 2R)-, (1'R, 2S)-, (1'S, 2R)- and (1'S, 2S)-$\alpha$-hydroxymetoprolol; (2R)- and (2S)-O-des-methylmetoprolol; and (2R)- and (2S)-metoprolol acid are major metabolites of (2R)-and (2S)-metoprolol, $\beta$-adrenergic antagonist. The focus of most chiral separation methods until now has been on determination of the enantiomeric parent drug. However, it is just as important to be able to follow the metabolism of the enantiomers and their possible chiral metabolites. Therefore, for the study of stereoselective metabolism and pharmacokinetics of metoprolol, the chiral separation of the enantiomers of metoprolol and its metabolites has been investigated using four chiral stationary phases, i.e., Chiralcel OD, Chiral-AGP, Cyclobond I and Sumichiral OA-4900 columns. Metoprolol acid was resolved only by Sumichiral OA-4900. Chiralcel OD provided the highest separation factor and resolution value for metoprolol and O-desmethylmetoprolol and partially resolved the four stereoisomers of $\alpha$-hydroxymetoprolol. Diastereomeric $\alpha$-hydroxymetoprolols were resolved using the coupled column chromatographic system of two chiral stationary phases, Sumichiral OA-4900 column and Chiralcel OD column.

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Influence of Temperature and pH on Fermentation Pattern and Methane Production in the Rumen Simulating Fermenter (RUSITEC)

  • Bhatta, R.;Tajima, K.;Kurihara, M.
    • Asian-Australasian Journal of Animal Sciences
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    • 제19권3호
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    • pp.376-380
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    • 2006
  • An experiment was conducted to study the effect of temperature and pH on in vitro nutrient degradability, volatile fatty acid profile and methane production. The fermenter used was the semi-continuous system, known as the rumen simulation technique (RUSITEC). Sixteen cylinders were used at one time with a volume of 800 ml, the dilution rate was set at 3.5%/hour, the infused buffer being McDougall's artificial saliva. Basal diet (9.6 g DM) used in RUSITEC consisted of (DM) 6.40 g Timothy hay, 1.86 g crushed corn and 1.34 g soybean meal. The food for the fermentation vessel was provided in nylon bags, which were gently agitated in the liquid phase. The experiment lasted for 17 d with all the samples taken during the last 5 d. Treatments were allocated at random to four vessels each and were (1) two temperature levels of $39^{\circ}C$ and $41^{\circ}C$ (2) two pH levels of 6.0 and 7.0. The total diet contained ($g\;kg^{-1}$ DM) 957 OM, 115 CP and $167MJ\;kg^{-1}$ (DM) GE. Although increase in temperature from $39^{\circ}C$ to $41^{\circ}C$ reduced degradation of major nutrients in vitro, it was non-significant. Interaction effect of temperature with pH also reflected a similar trend. However, pH showed a significant (p<0.05) negative effect on the degradability of all the nutrients in vitro. Altering the in vitro pH from 7 to 6 caused marked reduction in DMD from 60.2 to 41.8, CPD from 76.3 to 55.3 and GED from 55.3 to 35.1, respectively. Low pH (6) depressed total VFA production (61.9 vs. 34.9 mM) as well as acetate to propionate ratio in vitro (from 2.0 to 1.5) when compared to pH 7. Compared to pH 7, total gas production decreased from 1,841 ml to 1,148 ml at pH 6, $CO_2$ and $CH_4$ production also reduced from 639 to 260 ml and 138 to 45 ml, respectively. This study supported the premise that pH is one of the principal factors affecting the microbial production of volatile fatty acids and gas. Regulating the ruminal pH to increase bacterial activity may be one of the methods to optimize VFA production, reduce methane and, possibly, improve animal performance.

간세포 배양-약물대사를 위한 모델 연구 (I. Primary cultured hepatocytes as a key in vitro model to improve preclinical drug development)

  • 이경태
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1994년도 제2회 추계심포지움
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    • pp.135-140
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    • 1994
  • Over past decades, numerous in vitro model has been developed to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerful model to better elucidate drug behavior at an early stage of preclinical development such as : 1. the characterization of main biotransformation reactions. 2. the identification of phase I and phase II isozymes involved in such reactions 3. the evaluation of interspecies differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles 4. the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions 5. the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obstained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers.

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진세노사이드 $Rg_1$$Rb_1$의 흡수$\cdot$분포$\cdot$배설 및 대사에 관한 연구 (STUDIES ON THE ABSORPTION, DISTRIBUTION, EXCRETION AND METABOLISM OF GINSENOSIDE $Rg_1\;AND\;Rb_1$ IN RATS)

  • Takino Yoshio;Tanizawa Hisayuki;Odani Tsutomu
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 1984년도 학술대회지
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    • pp.169-183
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    • 1984
  • 인삼의 주된 사포닌으로서 Rg,과 Rb,을 흰쥐에 투여하였을 경우에 이들 물질이 흰쥐의 장기에 흡수 또는 분포되는 상태와 배설에 대하여 연구하였다. 진세노사이드 $Rg_{1}$은 경구 투여량의 약 $1.9{\%}$가 소화관의 상부에서 흡수되었으며, 투여한지 30분 후에 최고 혈중 농도에 이르렀고 조직에서는 1.5시간 걸렸다. 그러나 뇌에서는 확인되지 않았으며 뇨와 당즙에는 2 : 5의 비로 배설되었다. $Rb_{1}$을 100mg/kg 경구투여한 결과, 소화관에서는 거의 흡수가 되지 않았으며, 한편 정맥주사(5mg/kg)의 경우는 혈중 $Rb_{1}$의 농도가 지수적으로 감소하였으며, B-phase의 반감기는 14.5시간이었다. 정맥주사후 혈청과 조직에 장시간 잔존은 활성을 나탄내는 혈청단백과의 결합과 관련이 있는 것으로 사료되며 시간에 따라 뇨로 배설되나 담즙에서는 확인되지 않았다. $Rg_{1}$$Rb_{1}$을 경구투여한 후 TLC와 $^{13}C$-NMR을 이용하여 위와 대장에서의 분해 상태를 연구한 결과 위에서 $Rg_{1}$의 일부가 분해, 6종류의 분해 산물이 r-everse phase TLC상에서 관찰되었고 이들 분해 산물은 약산성 (0.1N HCl, $37^{\circ}C$) 조건하에서 $Rg_{1}$의 가수분해산물과 동일하였다. 한편, $Rb_{1}$ 경구투여후 위장에서 얻은 시료중에서 미확인 분해산물이 관찰되었으며, 이 분해산물은 약산성 조건하에서 $Rb_{1}$의 가수분해산물과는 상이하다는 사실을 확인하였다. 대장에서, $Rg_{1}$은 미생물 tetracycline-susceptible bacteria와 tetracycline-resist bacteria에 의해 $Rb_{1}$$F_{1}$으로 분해되었으며, $Rb_{1}$은 장내의 효소와 tetracycline-resistantant bacteria에 의해 Rd와 2 종류의 미확인 물질로 분해되었다.

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한국인 구강 편평세포암에서 Glutathione S-transferase와 CYP1A1 유전자의 다형성 (GENETIC POLYMORPHISMS OF THE GLUTATHIONE S-TRANSFERASE AND CYP1A1 GENES IN KOREAN ORAL SQUAMOUS CELL CARCINOMA)

  • 차인호;권종진;박광균
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제28권5호
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    • pp.364-371
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    • 2002
  • Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the polymorphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymorphisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozygote(m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic polymorphisms exist among different ethnic group and different types of human cancer.