https://doi.org/10.33573/ujoh2007.01.003
Gorovenko N.G.1, Zhurakhivska N.V.1-2, Basanets A.V.2, Podolska S.V.1
STUDYING THE ROLE OF SOME BIOMARKERS OF HEREDITARY SUSCEPTIBILITY AND RESISTANCE TO PNEUMOCONIOSIS IN COAL DUST EXPOSURE
1National Medical Academy for Post-Graduate Education named after P.L.Shupyk of MH of Ukraine, Kyiv
2Institute for Occupational Health of AMS of Ukraine, Kyiv
Full article (PDF), UKR
In recent years a search for new approaches to primary prevention and prognosis of coal workers pneumoconiosis (CWP) development, based on biomarkers determination, is under way. The biomarkers allow to determine mechanisms of individ¬ual susceptibility and resistance to coal dust exposure. The genes GSTs is one of biomarker candidates of the inherited pre-disposition to CWP.The ratio between the normal (norm) and null (0) alleles of the genes encoding glutatione-S-transferases M1 (GSTM1) and T1 (GSTT1) were investigated in 138 healthy miners (control group) and in 112 miners with CWP who had minimum 10 years of the underground work experience. The presence of GSTM 1 and GSTT1 genes was determined using multiplex PCR. The frequency of the GSTM1 (0/0) genotype in the population sample was significantly higher (55%) than in patients with CWP (41%; x2=4,31; P=0,038). For the GSTTI gene the similar data were not obtained. The frequency of the GSTT1 0/0 genotype in healthy miners (22,5%) was not significantly different from the patients with CWP (17%; x2=0,85; P=0,356). A significant preponderance of the compound homozygotes for the GSTM1 and GSTTI null alleles among healthy miners was observed. The frequency of the GSTM1 (0/0); GSTTI(0/0) among patients was 6,3%, while it was 16,7% in the control group (X2=5,4; P=0,02).The results indicate that the GSTTI null genotype does not influence the predisposition to CWP in this sample. The GSTM 1 normal genotype is associated with the risk of CWP development, whereas the genotypes GSTM1 (0/0) and GSTM1 (0/0); GSTTI(0/0) proved to be biomarkers in the resistance to the disease development.
Key words: miners, pneumoconiosis, genes, biomarkers, heredity
References
- Baraniv V.S., Aseev M.V., Baranova V.E. “Heny skhylnosti” i henetychnyy pasport//Priroda.- No 3.- S. 13-17.
- Horovenko N.H., Podolska S.V., Rossokha 3.1. Henetychni markery pidvyshchenoyi skhylnosti novonarodzhenykh do vynyknennya uskladnen u rannyomu neonatalnomu periodi//Sovrem. pedyatriya.- 2006,- T.2, No 11.-S. 172-176.
- Ebrakhimi M., Podol'skaya S.V., Gorovenko N.G. Polimorfizm genov glutation-S-transferaz M1 i T1 i faktory riska vozniknoveniya bronkhial'noy astmy//3b. nauk, prats' spívrobítnikív KMAPO ím. P.L.Shulika.- 2005.- Vip. 14, kn.5.- S. 118-130.
- Arand М., Muhlbauer R., Oesch F. et al. A multiplex polymerase chain reaction protocol for the simultaneously analysis of the Glutathione-S-transferаse GSTM1 and GSTT1 polymorphisms//Analytical Biochemistry.- 1996.- V.236.- P. 184-186. https://doi.org/10.1006/abio.1996.0153
- Autrip H. Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response//Mutat. Res.- 2000.- No 464.- P. 65-76. https://doi.org/10.1016/S1383-5718(99)00167-9
- Castranova V., Valiyathan V. Silicosis and coal workers' pneumoconiosis//Environ. Health Persp.-2000, -V. 108, No 4.- P. 675-684. https://doi.org/10.1289/ehp.00108s4675
- Castranova V. From coal mine dust to quartz: Mechanisms of pulmonary pathogenicity//Inhalation toxicol.— 2000.- V.2, No 10.-P. 7-14. https://doi.org/10.1080/08958370050164842
- Tоwnsend D.M., Tew K.D. The role of glutathione- S-transferase in anti-cancer drug resistance//Oncogene.- 2003,- No 22.- P. 7369-7375. https://doi.org/10.1038/sj.onc.1206940
- Eaton D.L., Bammler T.K. Concise Review of the Glutatione-S-Transferases and their Significance to Tоxicology//Toxicol, sci.- 1999.-No 49.-P. 156-164. https://doi.org/10.1093/toxsci/49.2.156
- Reszka Е., Wasowicz W. Significance of genetic polymorphisms in glutathione-S-transferase multigene family and lung cancer risk//Int. J. Occup. Med. Environ. Health.- 2001.- V. 14.- No 2.- P. 99-113.
- Freer A., Zhao L., Alldersea J. et al. Use of site- directed mutagenesis of allele-specific PCR primers to identify the GSTM 1 A. GSTM 1 B, GSTMI A. В and GSTM 1 null polymorphisms at the glutathione-S-transferase, GSTMI loots//Biochem.- 1993.- No 295,- P. 313-315. https://doi.org/10.1042/bj2950313
- Fryer A.A., Zhao L., Alldersea J. The glutatione- S-transferases: polymerase chain reaction studies on the frequency of the GSTM 1 0 genotype in patients with pituitary adenomas//Carcinogenesis.- 1993.- No 14,- P. 563-566. https://doi.org/10.1093/carcin/14.4.563
- Gao N.. Keane M.J., Ong T. et al. Effects of phospholipids surfactant on apoptosis induction by respirable quartz and kaolin in NR8383 rat pulmonary macrophages//Toxicol. Appl. Pharmacol.- 2001.- V.175.-P. 217-225. https://doi.org/10.1006/taap.2001.9249
- Hirvonen A. Polymorphisms of xenobiotic- metabolising enzymes and susceptibility to cancer// Environ. Health Perspect- 1999.-V.107, No 1.-P. 37-47. https://doi.org/10.1289/ehp.99107s137
- Kerb R., Brockmoller J., Sachse C., Roots I. Detection of the GSTM 1 0 allele by long potymerase chain reaction//Pharmacogenetics - 1999.-No 9.-P. 89-94. https://doi.org/10.1097/00008571-199902000-00012
- Malats N.. Camus-Radon F.V., Nyberg F. et al. Lung cancer risk in nonsmokers and GSTMI and GSTT1 genetic polymorphism//Cancer Epidemiol., Biomarkers & Prevention.- 2000.- V.9.- P. 827-833.
- Zhai R., Liu G., Ge X. et al. Genetic polymorphisms of MnSOD, GSTMI, GSTT1, and OGGI in coal workers' pneumoconiosis//Occup. Environ. Med.- 2002,- V.44. No 4.-P. 372-377. https://doi.org/10.1097/00043764-200204000-00019