Association of coding region single nucleotide polymorphism in cytochrome P4501A1 with susceptibility to childhood acute leukemia / 中华实用儿科临床杂志

Objective To investigate the single nucleotide polymorphism(SNP)in the coding region in cyto-chrome P4501 A1 (CYP1A1)gene and to evaluate the contributions of SNPs to acute lymphocytic leukemia(ALL)and acute myeloid leukemia(AML)susceptibility in children.Methods One hundred and twenty -one(male 76,female 45)children with acute leukemia were selected from Department of Hematology in Shenzhen Children′s Hospital,Zuyi Medical College between January 2007 and January 201 4 as the case study group,and the average age was 4.42 years old.Case study group included 1 01 (male 65,female 36,average age 4.38 years old)ALL children (ALL group)and 20(male 1 1 ,female 9,average age 4.66 years old)AML children(AML group).A total of 1 1 6(male 74,female 42) children with respiratory tract infections on health examination during the same period were selected as the control group and the average age was 3.93 years old.SNPs in the coding region in CYP1A1 gene were detected by reverse transcrip-tional(RT)-PCR -denaturing gradient gel elelctrphoresis(DGGE)combined with direct sequencing in the case study group and the control group.Results Only one SNP,A4889G,was screened in the open reading frame (ORF)of CYP1A1 gene in Chinese Han children and the G allele frequency of CYP1A1 gene in the case group,ALL group,AML group and the control group were 31 .4%,32.2%,27.5% and 38.8%.The CYP1A1 A4889G AG and AG +GG geno-type were linked with decreased risk of AML(OR =0.31 ,95%CI:0.1 1 -0.87,P =0.02;OR =0.35,95%CI:0.1 4 -0.93,P =0.03)especially in boys with AML(OR =0.1 2,95%CI:0.03 -0.60,P =0.01 ;OR =0.1 6,95%CI:0.04 -0.65,P =0.01 ),but the CYP1A1 A4889G polymorphism was not associated with the risk of ALL(P >0.05). The CYP1A1 A4889G allele frequency and the distribution of genotypes were significantly different from those reported in America,India,Korea,Brazil and Iran(all P <0.05).Conclusions CYP1A1 A4889G polymorphism may be not as-sociated with susceptibility to ALL,but may decrease the risk of childhood AML especially in boys with AML.In addi-tion,it may exhibit an ethnic difference.

Increased expression and activity of aryl hydrocarbon receptor in peripheral blood mononuclear cells from patients with rheumatoid arthritis / 中华微生物学和免疫学杂志

Objective To explore the significance of aryl hydrocarbon receptor (AhR) in patients with rheumatoid arthritis (RA) through detecting the levels of AhR and its response gene cytochrome P4501 A1 (CYP1 A1) in peripheral blood mononuclear cells (PBMCs).Methods Peripheral blood samples were collected from 35 patients with RA and 20 healthy subjects.The expression of AhR and CYP1A1 at mRNA level were detected by real-time PCR.The percentages of AhR-positive cells in PBMCs were detected by flow cytometry (FCM).The effects of leflunomide (LEF) on the expression of AhR and CYP1A1 were analyzed.The detailed clinical data of RA patients were recorded.The disease activity score (DAS) was calculated.Correlation analysis between AhR/CYP1A1 level and clinical data was conducted.Results (1) Both the expression of AhR at mRNA level and the percentage of AhR-positive cells in PBMCs from RA patients without LEF treatment were significantly higher than those from healthy subjects [(3.61±1.65) vs.(2.00±1.27),P=0.002; (34.21±11.30)％ vs.(18.83±7.32)％,P＜0.01].There were no statistically significant differences in the expression of AhR at mRNA level and the percentages of AhR-positive cells between patients with or without LEF treatment [(3.83 ± 1.62) vs.(3.61 ± 1.65),P =0.670 ; (36.69±10.61)％ vs.(34.21±11.30)％,P=0.462].(2) Non-LEF treatment group showed a higher relative expression of CYP1 A1 at mRNA level than that from control group [1.33 (0.08,7.86) vs.(0.62 ±0.29),z=-3.922,P＜0.01],but there was no statistical difference between LEF treatment group and non-LEF treatment group [(2.62±2.08) vs.1.33(0.08,7.86) z=-0.133,P=0.894].(3) Neither the expression of AhR and CYP1A1 at mRNA level nor the percentages of AhR-positive cells showed significant correlations with clinical data.Conclusion AhR was highly expressed in PBMCs from patients with RA,which might participate in the progression of rheumatoid arthritis.But the high expression of AhR did not reflect disease activity.Moreover,the treatment of LEF showed no significant influences on the expression of AhR and CYP1A1 in PBMCs from patients with RA.

Research on the relationship between lung cancer with CYP1A1,CYP1B1,VEGF,CAIX genes / 中国生化药物杂志

Cytochrome P 4501 A 1, Cytochrome P 4501 B 1,Vascular endothelial growth factorand carbonic anhydrase Ⅸ belong to the downstream genes of aryl hydrocarbon receptor (AhR)and hypoxia inducible factor 1(HIF-1)signaling pathways. The abnormal expression of those genes were regarded to associated with the occurrence,development and angiogenesis of lung cancer. In this paper, the relationship between CYP1 A 1,CYP1 B 1,VEGF,CAⅨgenes and lung cancer was summarized, which aims to provide new ideas for lung cancer research.

Effect of tetrachlorodibenzo-p-dioxin on the expression of cytochrome P4501A1 in human SZ95 sebocytes and its significance / 中华皮肤科杂志

Objective To estimate the effect of the enviromental pollutant 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD),a representative of the dioxin family,on the expression of cytochrome P4501A1 (CYP1A1) in cultured human immortalized SZ95 sebocytes in vitro,so as to improve understanding of the pathogenesis of chloracne.Methods SZ95 sebocytes were cultured with or without the presence of 10 nmol/L TCDD for two hours or three days.Real time fluorescence-based PCR was performed to quantify the mRNA expression of CYP1A1,immunohistochemistry and Western blot to determine the expression level of CYP1A1 protein,in the SZ95 cells.Chi-square test was done to compare the protein and mRNA expressions of CYP1A1 between untreated and treated SZ95 cells.Results Real time PCR showed that the mRNA expression of CYP1A1 was low in SZ95 sebocytes,and increased by 5.622 times after 2-hour treatment with TCDD(P ＜ 0.05).Immunohistochemistry revealed a weak expression of CYP1A1 protein in the cytoplasm and nuclei of untreated SZ95 sebocytes,which was also significantly enhanced by the TCDD treatment.Western blot results showed that the relative expression level of CYP1A1 protein was 4.233 ± 0.252 in SZ95 sebocytes treated by TCDD for three days,significantly higher than that in untreated sebocytes(0.123 ± 0.208,P ＜ 0.05).Conclusions There is a low expression of CYP1A1 mRNA and protein in SZ95 sebocytes,which can be upregulated by TCDD,suggesting that the CYP1A1 gene is a downstream target of the aryl hydrocarbon receptor responsible for the abnormal differentiation of human sebocytes.

The benzo(a)pyrene-induced mRNA expression of aromatic hydrocarbon receptor and cytochrome P4501A1 genes in rat liver / 西安交通大学学报·英文版

Objective: To study the benzo(a)pyrene (B[a]P)-induced mRNA expression of aromatic hydrocarbon receptor (AHR) and cytochrome P4501A1 (CYP1A1) genes in rat liver. Methods: Rats were injected intraperitoneally with 5, 10 and 15 mg/kg of B[a]P. The total RNAs were extracted from rat livers by RNA purification kit, and the mRNA expression of AHR and CYP1A1 genes was determined by reverse transcription polymerase chain reaction (RT-PCR). β-actin was used as the internal control. The mRNA expression of both AHR and CYP1A1 genes was measured at indicated time points (24, 48 and 72 h) after B[a]P treatment at three different concentrations (5, 10 and 15 mg/kg). Results: The mRNA expression of AHR gene increased in a time-dependent manner at the concentration of 10 mg/kg but not at 5 and 15 mg/kg of B[a]P. The mRNA expression of CYP1A1 gene differed significantly at 48 h and 24 h in rat livers treated with 10 and 15 mg/kg dosage of B[a]P. The mRNA expression of AHR and CYP1A1 genes increased with B[a]P treatment in a concentration-dependent manner. The time-dependent increase in mRNA expression was shown by AHR but not by CYP1A1 gene with B[a]P (10 mg/kg) treatment. Conclusion: This study demonstrates that toxic B[a]P increases the mRNA expression of both AHR and CYP1A1 genes in vivo, suggesting that B[a]P may play a role in cancer genesis by this way.

The benzo(a)pyrene-induced mRNA expression of aromatic hydrocarbon receptor and cytochrome P4501A1 genes in rat liver / 药物分析学报

Objective To study the benzo(a)pyrene (B[a]P)-induced mRNA expression of aromatic hydrocarbon receptor (AHR) and cytochrome P4501A1 (CYP1A1) genes in rat liver. Methods Rats were injected intraperitoneally with 5, 10 and 15mg/kg of B[a]P. The total RNAs were extracted from rat livers by RNA purification kit, and the mRNA expression of AHR and CYP1A1 genes was determined by reverse transcription polymerase chain reaction (RT-PCR). β-actin was used as the internal control. The mRNA expression of both AHR and CYP1A1 genes was measured at indicated time points (24, 48 and 72h) after B[a]P treatment at three different concentrations (5, 10 and 15mg/kg). Results The mRNA expression of AHR gene increased in a time-dependent manner at the concentration of 10mg/kg but not at 5 and 15mg/kg of B[a]P. The mRNA expression of CYP1A1 gene differed significantly at 48h and 24h in rat livers treated with 10 and 15mg/kg dosage of B[a]P. The mRNA expression of AHR and CYP1A1 genes increased with B[a]P treatment in a concentration-dependent manner. The time-dependent increase in mRNA expression was shown by AHR but not by CYP1A1 gene with B[a]P (10mg/kg) treatment. Conclusion This study demonstrates that toxic B[a]P increases the mRNA expression of both AHR and CYP1A1 genes in vivo, suggesting that B[a]P may play a role in cancer genesis by this way.

Reproductive Development and Pulmonary CYP1A1 Levels in Mice Offspring Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) During Lactation / 环境与健康杂志

Objective To explore the effect of lactational TCDD exposure alone on growing development and cytochrome P4501A1(CYP1A1) in mice offspring. Methods Mature Kunming mice (clean animal,No.604017) were divided to 2 treatment groups (40 and 20 ?g /kg bw TCDD),2 vehicle controls and 1 normal control. There were 3 maternal mice and 25-28 pups in each group. Maternal mice were administered TCDD by intraperitoneal injection in three times on post-parturition days 1,3,5,and the mice offspring were exposed to TCDD by maternal milk. The changes of body weight and the development of reproductive system were observed. The pups were sacrificed on postnatal days (PND) 35,and CYP1A1 expression in the lungs of mice offspring were measured by immunohistochemistry. Results The average body weight of mice offspring in 2 TCDD treatments decreased significantly from PND14 (P

Lung cancer andCYP1A1 orGSTM1 polymorphisms

Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that in clude various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms inGSTM1 (a member of GST) andCYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in theGSTM1 andCYP1A1 genes and their relation to lung cancer susceptibility.

Lung Cancer and \it{CYP1A1} or \it{GSTM1} Polymorphisms

Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that include various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms in GSTM1 (a member of GST) and CYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in the GSTM1 and CYP1A1 genes and their relation to lung cancer susceptibility.

Genetic Polymorphism of Cytochrome P4501A1 Exon 7 and Glutathione S-Transferase M1 in the Head and Neck Squamous Cell Carcinoma Patients / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: An individual difference in susceptibility to chemically induced carcinomas is in part ascribed to genetic differences of metabolic activity of environmental procarcinogens. The cytochrome P450 family (CYPs) and glutathione S-transferase (GST) have been reported to be associated with human cancers related with smoking. The purpose of this study was to determine the frequencies of the genotypes of CYP1A1 and GSTM1 genes in healthy control of Koreans and to identify the high-risk genotypes of these metabolic genes in head and neck cancer patients. MATERIALS AND METHOD: The genetic polymorphism of CYP1A1 exon 7 and GSTM1 genes were analysed in a group of 115 healthy Koreans and 107 head and neck squamous cell carcinoma patients using allelic-specific polymerase chain reaction. RESULTS: The genotypes of CYP1A1 exon 7 (Ile/Ile, Ile/Val and Val/Val) were 59.1%, 36.5% and 4.4%, respectively, in the healthy control group, and 57.0%, 31.8% and 11.2%, respectively, in the cancer patients . The distributions of GSTM1 [GSTM1 (-), GSTM1 (+)] in healthy control group were 46.1%, 53.9% respectively, and 53.3%, 46.7%, respectively, in the cancer patients. The relative risk (odds ratio) for combination of CYP1A1 Val/Val and GSTM1 (-) genotype was estimated to be 5.17, taking the risk of combined genotype Ile/Ile and GSTM1 (+) as a reference in cancer patients. CONCLUSION: These results suggest that the genetic polymorphisms of CYP1A1 exon 7 and GSTM1 were an important major factor in determining the individual susceptibility to head and neck squamous cell carcinoma in Koreans.