An Association Between BPDE-like DNA Adduct Levels and CYP1A1 and GSTM1 Polymorphisma in Pterygium

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2010 Aug 12

PMID 20700368

Citations 4

Authors

Jai-Nien Tung

Heng-Hsiung Wu

Chun-Chi Chiang

Yi-Yu Tsai

Ming-Chih Chou

Huei Lee

Ya-Wen Cheng

Affiliations

Soon will be listed here.

Abstract

Purpose: Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), an ultimate metabolite of benzo[a]pyrene, attacks deoxyguanosine to form a BPDE-N2-dG adduct resulting in p53 mutations. Both cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) have been demonstrated to be involved in the metabolism of polycyclic aromatic hydrocarbons. The relationship between BPDE-like DNA adduct levels and CYP1A1 and GSTM1 gene polymorphisms in pterygium is not clear. Therefore, BPDE-like DNA adducts and CYP1A1 and GSTM1 polymorphisms were detected in this study to provide more molecular evidence to understand the cause of BPDE-like DNA adduct formation in pterygium.

Methods: In this study, immunohistochemical staining using a polyclonal antibody on BPDE-like DNA adducts was performed on 103 pterygial specimens. For the analysis of CYP1A1 and GSTM1 polymorphisms, DNA samples were extracted from epithelial cells and then subjected to restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) for the determination of mutation and genotype of CYP1A1 and GSTM1.

Results: BPDE-like DNA adducts were detected in 33.0% (34/103) of the pterygium samples. The differences in DNA adduct levels were associated with the genetic polymorphisms of CYP1A1 but not GSTM1. Additionally, the risk of BPDE-like DNA adduct formation for patients with CYP1A1 m1/m2 (C/T) andm2/m2 (T/T) was 9.675 fold higher than that of patients with CYP1A1 m1/m1 (C/C) types (p=0.001, 95% Confidence Interval 2.451-38.185).

Conclusions: Our data provide evidence that the BPDE-like DNA adduct formation in pterygium samples was associated with CYP1A1 polymorphisms.

Citing Articles

Unravelling the molecular tapestry of pterygium: insights into genes for diagnostic and therapeutic innovations.

Gupta M, Arya S, Agrawal P, Gupta H, Sikka R Eye (Lond). 2024; 38(15):2880-2887.

PMID: 38907016 PMC: 11461965. DOI: 10.1038/s41433-024-03186-y.

MicroRNA-215 Regulates Fibroblast Function: Insights from a Human Fibrotic Disease.

Lan W, Chen S, Tong L Cell Cycle. 2015; 14(12):1973-84.

PMID: 25565137 PMC: 4613146. DOI: 10.1080/15384101.2014.998077.

CYP1A1 protein activity is associated with allelic variation in pterygium tissues and cells.

Peng M, Tsai Y, Chiang C, Huang Y, Chou M, Yeh K Mol Vis. 2012; 18:1937-43.

PMID: 22876118 PMC: 3413426.

CYP1A1 gene polymorphisms as a risk factor for pterygium.

Young C, Lo Y, Tsai Y, Shih T, Lee H, Cheng Y Mol Vis. 2010; 16:1054-8.

PMID: 20596254 PMC: 2893055.

References

Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K . Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev. 2000; 9(1):3-28. View

Ketterer B, Harris J, Talaska G, Meyer D, Pemble S, Taylor J . The human glutathione S-transferase supergene family, its polymorphism, and its effects on susceptibility to lung cancer. Environ Health Perspect. 1992; 98:87-94. PMC: 1519626. DOI: 10.1289/ehp.929887. View

Tan D, Lim A, Goh H, Smith D . Abnormal expression of the p53 tumor suppressor gene in the conjunctiva of patients with pterygium. Am J Ophthalmol. 1997; 123(3):404-5. DOI: 10.1016/s0002-9394(14)70141-2. View

Sundberg K, Seidel A, Mannervik B, Jernstrom B . Detoxication of carcinogenic fjord-region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferase P1-1 variants and glutathione. FEBS Lett. 1998; 438(3):206-10. DOI: 10.1016/s0014-5793(98)01291-5. View

HILGERS J . Pterygium: its incidence, heredity and etiology. Am J Ophthalmol. 1960; 50:635-44. DOI: 10.1016/0002-9394(60)90245-2. View

Dushku N, HATCHER S, Albert D, Reid T . p53 expression and relation to human papillomavirus infection in pingueculae, pterygia, and limbal tumors. Arch Ophthalmol. 1999; 117(12):1593-9. DOI: 10.1001/archopht.117.12.1593. View

Cheng L, Eicher S, Guo Z, Hong W, Spitz M, Wei Q . Reduced DNA repair capacity in head and neck cancer patients. Cancer Epidemiol Biomarkers Prev. 1998; 7(6):465-8. View

Lai T, Tsai Y, Cheng Y, Chiang C, Lee H, Chou M . An association between BPDE-like DNA adduct levels and P53 gene mutation in pterygium. Mol Vis. 2007; 12:1687-91. View

Lodovici M, Luceri C, Guglielmi F, Bacci C, Akpan V, Fonnesu M . Benzo(a)pyrene diolepoxide (BPDE)-DNA adduct levels in leukocytes of smokers in relation to polymorphism of CYP1A1, GSTM1, GSTP1, GSTT1, and mEH. Cancer Epidemiol Biomarkers Prev. 2004; 13(8):1342-8. View

10.

Kawajiri K, Nakachi K, Imai K, Yoshii A, Shinoda N, Watanabe J . Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene. FEBS Lett. 1990; 263(1):131-3. DOI: 10.1016/0014-5793(90)80721-t. View

11.

Tsai Y, Bau D, Chiang C, Cheng Y, Tseng S, Tsai F . Pterygium and genetic polymorphism of DNA double strand break repair gene Ku70. Mol Vis. 2007; 13:1436-40. View

12.

Hussain S, Amstad P, Raja K, Sawyer M, Hofseth L, Shields P . Mutability of p53 hotspot codons to benzo(a)pyrene diol epoxide (BPDE) and the frequency of p53 mutations in nontumorous human lung. Cancer Res. 2001; 61(17):6350-5. View

13.

London S, Daly A, Leathart J, Navidi W, Idle J . Lung cancer risk in relation to the CYP2C9*1/CYP2C9*2 genetic polymorphism among African-Americans and Caucasians in Los Angeles County, California. Pharmacogenetics. 1996; 6(6):527-33. DOI: 10.1097/00008571-199612000-00006. View

14.

Kao S, Wu C, Lin S, Chang C, Wong Y, Chi L . Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use. J Oral Pathol Med. 2002; 31(9):505-11. DOI: 10.1034/j.1600-0714.2002.00158.x. View

15.

Sato M, Sato T, Izumo T, Amagasa T . Genetic polymorphism of drug-metabolizing enzymes and susceptibility to oral cancer. Carcinogenesis. 1999; 20(10):1927-31. DOI: 10.1093/carcin/20.10.1927. View

16.

McWILLIAMS J, Sanderson B, Harris E, Henner W . Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 1995; 4(6):589-94. View

17.

Pemble S, SCHROEDER K, Spencer S, Meyer D, Hallier E, Bolt H . Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J. 1994; 300 ( Pt 1):271-6. PMC: 1138152. DOI: 10.1042/bj3000271. View

18.

Hainaut P, Vahakangas K . p53 as a sensor of carcinogenic exposures: mechanisms of p53 protein induction and lessons from p53 gene mutations. Pathol Biol (Paris). 1998; 45(10):833-44. View

19.

Shimada T, Yun C, Yamazaki H, GAUTIER J, Beaune P, Guengerich F . Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens. Mol Pharmacol. 1992; 41(5):856-64. View

20.

Kuo C, Cheng Y, Chen C, Lee H . Correlation between the amounts of polycyclic aromatic hydrocarbons and mutagenicity of airborne particulate samples from Taichung City, Taiwan. Environ Res. 1998; 78(1):43-9. DOI: 10.1006/enrs.1998.3838. View