• Journal of Preventive Medicine and Public Health
• /
• 제32권2호
• /
• pp.123-129
• /
• 1999

1997년 3월부터 1998년 6월까지 충북대학교병원 내과에 입원하여 치료를 받은 폐암환자 98명과 암 아닌 다른 질환을 가진 대조군 98명을 대상으로 흡연, 음주, 여러 가지 질병과거력 등을 포함한 생활습관과, GSTM1과 GSTT1, 그리고 CYP1A1, CYP1E1 유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다. 1. GSTM1의 결손은 환자군이 67.01%, 대조군이 58.16%로 확인되었으며, OR(95% CI)이 1.46(0.82-2.62)으로 폐암 발생에 대해 유의한 영향을 미치지 않는 것으로 나타났다. 2. GSTT1의 결손은 환자군이 58.76%, 대조군이 50.00%로 확인되었으며, OR (95% CD가 1.43(0.81-2.51)으로 폐암 발생과 관련이 없는 것으로 나타났다. 3. CYP1A1 유전자 다형성은 Ile/Ile, Ile/Val, Val/Val 환자군이 각각 59.18%, 35.71%, 5.10%, 대조군이 각각 52.04%, 45.92%, 2.04%로 CYP1A1 유전자 다형성과 폐암 위험도 사이의 관련성은 유의하지 않은 것으로 나타났다$(x^2trend=0.253,\;p-value>0.05)$. 4. CYP1E1 유전자 다형성은 c1/c1, c1/c2, c2/c2 형 이 환자군에서 각각 50.00%, 42.86%, 7.14%, 대조군에서 각각 66.33%, 30.61%, 3.06%로 CYP1E1 활성이 폐암 발생에 유의한 영향을 미치는 것으로 나타났다$(x^2trend=5.783,\;p-value<0.05)$. 특히 환자군이 대조군에 비하여 아주 드문 대립유전자인 c2형이 더 많은 것으로 나타났다. 5. 폐암과 밀접한 연관이 있는 흡연습관의 OR(95% CI)이 3.03(1.58-5.81)으로 확인되어, 폐암의 위험인자로 재확인 되었다. 6. GSTM1, GSTT1, CYP1A1, CYP2-E1과 흡연습관을 포함한 다변량 분석에서 흡연습관만이 유의한 폐암의 위험인자로 나타났다. 이 결과로부터 위의 4가지 유전자의 다형성이 폐암발생에 미치는 영향은, 흡연을 포함한 환경적 요인에 비하여 크지 않을 것으로 판단된다.

• 환경생물
• /
• 제21권1호
• /
• pp.1-7
• /
• 2003

CYP1A 유전자는 cytochrome P450 약물대사효소에 속하며 다이옥신 등의 내분비계 장애물질에 의해 농도 의존적으로 유도되어 환경오염물질에 의해 유도되는 특성을 이용하여 환경오염물질에 대해 반응하는 생물체의 유전자 발현 변화뿐만 아니라 이를 토대로 특정지역의 환경오염에 관한 정보를 얻을 수 있다. 본 논문에서는 수서환경오염과 관련하여 CYP1A유전자의 유용성을 다각도로 논의하였다.

• 한국어병학회지
• /
• 제23권2호
• /
• pp.245-254
• /
• 2010

뱀장어 간세포 배양을 이용하여 cytochrome P4501A (CYP1A) 유전자 발현에 대한 중금속들의 영향에 대해 조사하였다. 첫째, CYP1A mRNA 발현에 대한 benzo[$\alpha$]pyrene (B[a]P)의 농도별 조사에서, B[$\alpha$]P $10^{-8}\sim10^{-5}$ M의 농도로 배양액에 첨가하여 배양한 후 세포를 수거하여 RT-PCR 방법으로 CYP1A mRNA 발현량을 조사하였다. CYP1A mRNA 발현은 B[$\alpha$농도 의존적으로 유도되었으며, $10^{-7}$ M 농도부터 통계적으로 유의차를 나타냈다 (p<0.05). 둘째로 뱀장어 간세포에 B[a]P ($10^{-5}$ M)와 카드뮴 ($10^{-6}$, $10^{-5}$ M)을 각각 또는 함께 첨가하여 CYP1A mRNA 발현을 조사하였다. 카드뮴을 첨가한 그룹은 vehicle에 비해 CYP1A 발현의 억제가 관찰되었으며, 고농도($10^{-5}$M)의 카드뮴에서 더 많이 억제되었다. 또한 B[$\alpha$]P와 카드뮴을 함께 처리한 그룹에서도 CYP1A 유전자 발현은 B[$\alpha$]P 단독 처리에 비해 현저한 억제가 관찰되었다. 셋째로, in vivo에서 B[a]P를 주사한 뱀장어의 배양 간세포를 이용하여 CYP1A 유전자 발현에 대한 중금속들의 영향을 조사하였는데, 뱀장어에 10mg/kg의 B[$\alpha$]P를 주사한 후, 48시간 후에 간을 채취하여 간세포 배양을 하였다. 카드뮴, 구리, 납 및 아연 ($10^{-6}$, $10^{-5}$ M) 등을 각각 배양액에 첨가하여 2일간 배양한 후 CYP1A mRNA 발현량을 조사하였다. 이미 B[$\alpha$]P 처리에 의해 CYP1A 발현이 유도된 대조구 (vehicle)에 비해 중금속들이 첨가된 모든 그룹에서 CYP1A 유전자 발현 억제가 관찰되었다. 본 연구는 여러 어종에서 CYP1A 유전자 발현에 대한 중금속들의 영향 및 중금속 독성을 연구하는데 매우 중요한 기초 자료로 활용되어질 것이다.

• Genomics & Informatics
• /
• 제7권4호
• /
• pp.187-194
• /
• 2009

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5673-5679
• /
• 2014

Background: Previous published data on the association between CYP1A2 rs762551, rs2069514, rs2069526, and rs2470890 polymorphisms and lung cancer risk have not allowed a definite conclusion. The present meta-analysis of the literature was performed to derive a more precise estimation of the relationship. Materials and Methods: 8 publications covering 23 studies were selected for this meta-analysis, including 1,665 cases and 2,383 controls for CYP1A2 rs762551 (from 8 studies), 1,456 cases and 1,792 controls for CYP1A2 rs2069514 (from 7 studies), 657 cases and 984 controls for CYP1A2 rs2069526 (from 5 studies) and 691 cases and 968 controls for CYP1A2 rs2470890 (from 3 studies). Results: When all the eligible studies were pooled into the meta-analysis for the CYP1A2 rs762551 polymorphism, significantly increased lung cancer risk was observed in the dominant model (OR=1.21, 95 % CI=1.00-1.46). In the subgroup analysis by ethnicity, significantly increased risk of lung cancer was observed in Caucasians (dominant model: OR=1.29, 95%CI=1.11-1.51; recessive model: OR=1.33, 95%CI=1.01-1.75; additive model: OR=1.49, 95%CI=1.12-1.98). There was no evidence of significant association between lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. Conclusions: In summary, this meta-analysis indicates that the CYP1A2 rs762551 polymorphism is linked to an increased lung cancer risk in Caucasians. Moreover, our work also points out the importance of new studies for rs2069514 associations in lung cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the rs2069514 polymorphism in lung cancer development.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권6호
• /
• pp.3925-3929
• /
• 2013

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

• 대한임상검사과학회지
• /
• 제54권4호
• /
• pp.316-324
• /
• 2022

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy in women of reproductive age. The genetics of PCOS is heterogeneous with the involvement of number of genes in the steroid synthesis pathway. The CYP11B2 encodes aldosterone synthase and the genetic variants might increase aldosterone secretion in PCOS cases. CYP1A1 is known to enhance the intraovarian catechol estrogen production and thus the propensity for PCOS. The present case-control study analyzed a total of 619 females for CYP11B2 (rs1799998) and CYP1A1 (rs4646903) polymorphisms. Obesity was examined according to body mass index (BMI) and waist hip ratio (WHR) categorization. Biochemical (lipid profile) analysis was performed in PCOS females. BMI (P=0.0001) and WHR (P=0.0001) revealed a statistically significant difference between PCOS cases and controls. The overall levels of triglycerides were higher in PCOS females. The genotype frequency distribution of CYP11B2 (rs1799998) polymorphism revealed statistically significant difference between PCOS cases and controls (P=0.017). However, CYP1A1 (rs4646903) polymorphism did not showed any association with PCOS. The present case-control association analysis is first from our region for CYP1A1 and CYP11B2 polymorphisms and is suggestive of genetic predisposition of steroidogenic genes among PCOS patients in the North-Indian Punjabi females.

• 대한예방한의학회지
• /
• 제16권3호
• /
• pp.129-137
• /
• 2012

Objective : Herb-drug interactions have become an important issue because of the consumption of herbal remedies has increased in the world. Yangguksanhaw-tang (Liang ge san huo-tang) and Taeumjowi-tang (Tai yin tiao wei-tang) are typical herbal formulas on Sasang constitution medicine (four-constitution medicine). This study was aimed at evaluating the effects of Yangguksanhaw-tang and Taeumjowi-tang on drug metabolizing enzymes, cytochrome P450 (CYP450) isozymes. Methods : Vivid$^{(R)}$ CYP450 Screening Kits were used to measure of CYP3A4, CYP2C19, CYP2D6 and CYP2E1 activities. This method is based on the use of fluorescent CYP450 substrates that are efficiently metabolized by specific CYP450 isozymes to yield a product with altered fluorescent properties. The percent inhibitions of CYP450s by herbal formulas were calculated. Results : Yangguksanhaw-tang inhibited CYP2C19 and CYP2E1 activities higher than that other CYP450 isozymes. The $IC_{50}$ values of CYP2C19 and CYP2E1 were 159.83 ${\mu}g/mL$ and 261.40 ${\mu}g/mL$, respectively. The CYP2E1 activity was inhibited ($IC_{50}=215.17{\mu}g/mL$) higher than that other CYP450 isozymes by Taeumjowi-tang. Conclusions : These results suggest that Yangguksanhaw-tang may inhibit the metabolism of co-administered drugs whose primary route of metabolism is via CYP2C19 or CYP2E1. Taeumjowi-tang could inhibit the metabolism of co-administered drugs, which are substrates for CYP2E1. Therefore, co-administration of the herbal formulas and other conventional drugs should be undertaken with care.

• Toxicological Research
• /
• 제31권4호
• /
• pp.339-345
• /
• 2015

CYP1A1 is a phase I xenobiotic-metabolizing enzyme whose expression is mainly driven by AhR. Endosulfan is an organochlorine pesticide used agriculturally for a wide range of crops. In this study, we investigated the effect of endosulfan on CYP1A1 expression and regulation. Endosulfan significantly increased CYP1A1 enzyme activity as well as mRNA and protein levels. In addition, endosulfan markedly induced XRE transcriptional activity. CH-223191, an AhR antagonist, blocked the endosulfan-induced increase in CYP1A1 mRNA and protein expression. Moreover, endosulfan did not induce CYP1A1 gene expression in AhR-deficient mutant cells. Furthermore, endosulfan enhanced the phosphorylation of calcium calmodulin (CaM)-dependent protein kinase (CaMK) and protein kinase C (PKC). In conclusion, endosulfan-induced up-regulation of CYP1A1 is associated with AhR activation, which may be mediated by PKC-dependent pathways.

• 한국환경성돌연변이발암원학회지
• /
• 제24권3호
• /
• pp.128-136
• /
• 2004

CYP1A1 is known to be inducible by xenobiotic compouds such as polyciclic aromatic hydrocarbons(PAHs) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). These chemicals have been identified worldwide and can have a significant impact on the human health and well being of human and wildlife. Given these issues, the detection and quantification of these chemicals in biological, environmental and food samples is important. First, we investigated the effect of on CYP1A1 promoter activity, 7-ethoxyresorufin-O-deethylase(EROD) activity and CYP1A1 mRNA expression induced by benzo(k)fluoranthene(B(k)F) in MCF-7 cells. We found that B(k)F significantly up-regulates the level of CYP1A1 prompter activity, EROD and CYP1A1 mRNA. When cells were treated with genistein, it was not changed that EROD and CYP1A1 mRNA, compared to that of control. However, genistein inhibited the B(k)F-induced CYP1A1 promoter activity and mRNA level at high concentration. Furthermore, in this study, effects of HDAC(histone deacetvlase) inhibitors on human prostate cancer cells proliferation were examined. HC-toxin, SAHA and TSA inhibited cell proliferation in PC3 cells. A novel HDAC inhibitor, IN2001 also suppressed the growth of PC3 cells. And IN2001 and SAHA increased S phase and G2/M phase at 12 hrs treatment but cells were arrested G0/G1 phase at 45 hrs treatment. The HC-toxin treatment for 24 hrs and 48 hrs increased G0/G1 at low concentration ($0.1\mu\textrm{m}$) but increased G2/M at more than concentration of $1\mu\textrm{m}$. TSA increased G2/M phase. These findings height the possbility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of prostate cancer.