Influence of xenobiotic detoxication gene polymorphisms and experience on the level of accumulation of dioxins in Emercom of Russia employees

Relevance. Occupational activities of firefighters are considered extreme. Toxic combustion products are the most dangerous. Among these products, dioxins and dioxin-like compounds are particularly dangerous due to their ability to accumulate in the body.

Intention is to analyze the content of toxic combustion products in atmospheric air during and after fires of various locations, as well as to evaluate dioxin concentrations in the blood plasma of employees of the Federal Firefighting Service of the Emercom of Russia, depending on the polymorphic variants of xenobiotic detoxification genes and professional experience.

Methodology. To assess accumulation of dioxins in the body of firefighters with different polymorphic variants of xenobiotic detoxification genes, atmospheric air at different locations of fires was assessed for toxic combustion products. Accumulation of dioxins in the body of firefighters was analyzed depending on the polymorphisms of xenobiotic detoxification genes and work experience. 350 employees of the Federal Firefighting Service of the Emercom of Russia were examined, of them there were 234 firefighters and 116 supervisory staff involved in the investigations at the fire sites. The control group consisted of 82 rescue workers who were not directly involved in fire fighting. The examined individuals aged (32.2 ± 9.5) years.

Results and Discussion. The data obtained indicate that high concentrations of dioxins in surface air at the fire site persist for more than 2 weeks, while the maximum permissible concentration is increased 4.5-10-fold. The highest concentration of dioxins is observed during fires in industrial enterprises and in residential buildings. According to the analysis of the dioxins in the blood of the Federal Firefighting Service employees and the control group, concentrations of individual chemical compounds among the employees of the Federal Firefighting Service were 2–7 times higher and 15 times higher in terms of the dioxin equivalent compared to the control group (p <0.05). High concentrations of dioxins were also revealed in the blood of supervisory staff. Analysis of the dioxins in the blood of the staff of the Federal Firefighting Service, EMERCOM of Russia showed that increased length of service correlated with dioxin concentrations in the blood: variations in chemical compounds reached 2.3–6.8 times (p <0.05) between those with 0–1 year vs 6 years or more experience and 1.3–1.7 times (p <0.05) between those with 2–5 years vs 6 years and more experience. Concentrations of dioxins in the blood plasma of employees of the Federal Firefighting Service of the Emercom of Russia were assessed depending on the polymorphic variants of xenobiotic detoxification genes and professional experience. A group of individuals carrying the combination of the EPHX1 Tyr / Tyr, CYP1A1 A / A, GSTT1 I / I, GSTM1 I / I, GSTP1 A / A, GSTP1 C / C genotypes was revealed: their dioxin concentrations in the blood were as low as 25% of that among other groups despite length of service.

Conclusion Genotyping of firefighters will help arrange timely measures to detoxify dioxins, especially in carriers of minor alleles of xenobiotic biotransformation genes, in order to reduce morbidity and increase professional longevity.

1. Basharin V.A., Grebenyuk A.N., Markizova N.F. [et al.]. Khimicheskie veshchestva kak porazhayushchii faktor pozharov [Chemicals as fires damaging factor]. Voenno-meditsinskii zhurnal [Military medical journal]. 2015. Vol. 336, N 1. Pp. 22–28. (In Russ.)

2. Grigoryeva S.A., Nikitina V.A., Revazova Yu.A. Svyaz’ allel’nykh variantov genov detoksikatsii ksenobiotikov s tsitogeneticheskim otvetom na deistvie mutagena [Relationship of the allelic types of xenobiotic detoxification genes to the cytogenetic response to a mutagen]. Gigiena i sanitariya [Hygiene & Sanitation]. 2007. N 5. Pp. 62–63. (In Russ.)

3. Gumerova G.I., Gogol’ E.V., Sibgatullina O.S. Immunofermentnye i biologicheskie metody opredeleniya dioksinov [Enzyme-linked and biological methods for the determination of dioxins] // Khimiya i inzhenernaya ekologiya [Chemistry and Environmental Engineering] : Scientific. Conf. Proceedings. Kazan’. 2017. Pp. 250–253. (In Russ.)

4. Dyakovich M.P., Shevchenko O.I. Mediko-psikhologicheskie posledstviya vozdeistviya faktorov pozhara na OAO «Irkutskkabel’» na pozharnykh likvidatorov [Medical-psychological consequences of exposure to fire factors among the fire fighters-liquidators at the Company “Irkutskcable”]. Meditsina truda i promyshlennaya ekologiya [Occupational medicine and industrial ecology]. 2008. N 1. Pp. 29–35. (In Russ.)

5. Evdokimov V.I., Sannikov M.V., Kharchenko N.N. Algoritm poiska publikatsii v Rossiiskom indekse nauchnogo tsitirovaniya o zabolevaemosti sotrudnikov MChS Rossii i drugikh professional’nykh grupp [An algorithm for searching publications in Russian Science Citation Index on morbidity in Russia Emercom specialists and other occupation groups]. Mediko-biologicheskie i sotsial’no-psikhologicheskie problemy bezopasnosti v chrezvychaynykh situatsiyakh [Medico-Biological and Socio-Psychological Problems of Safety in Emergency Situations]. 2013. N 3. Pp. 74–86. DOI: 10.25016/2541-7487-20130-3-74-86. (In Russ.)

6. Karamova L.M., Basharova G.R. Klinicheski bezopasnyi uroven’ dioksinov [Clinically safe level of dioxines]. Meditsina truda i promyshlennaya ekologiya [Occupational medicine and industrial ecology]. 2012. N 2. Pp. 45–48. (In Russ.)

7. Kuznetsova N.B., Kuznetsov P.E. Veroyatnyi mekhanizm induktsii tsitokhroma r-450(448) polikhlorirovannymi dibenzo-p-dioksinami [The probable mechanism of induction of cytochrome r-450 (448) by polychlorinated dibenzo-p-dioxins]. Auditorium. 2018. N 1. Pp. 1–7. (In Russ.)

8. Limborskaya S.A., Verbenko D.A., Khrunin A.V., Slominskii P.A. Etnicheskaya genomika narodonaseleniya Vostochnoevropeiskogo regiona [Ethnic Genomics of the Population of the East European Region]. Molekulyarnyi polimorfizm cheloveka: individual’noe raznoobrazie biomakromolekul [Molecular Human Polymorphism: Individual Diversity of Biomacromolecules]. Ed. S.D. Varfolomeev. Moskva. 2007. Pp. 707–749. (In Russ.)

9. Limborskaya S.A., Khusnutdinova E.K., Balanovskaya E.V. Etnogenomika i genogeografiya narodov Vostochnoi Evropy [Ethnogenomics and genogeography of the peoples of Eastern Europe]. Moskva. 2002. 261 p. (In Russ.)

10. Lotfullina E.R., Gumerova G.I. Gibridnye metody opredeleniya dioksinovю Khimiya i inzhenernaya ekologiya [Hybrid methods for the determination of dioxins]: Scientific. Conf. Proceedings. Kazan’. 2017. Pp. 292–296. (In Russ.)

11. Markizova N.F., Preobrazhenskaya T.N., Basharin V.A., Grebenyuk A.N. Toksichnye komponenty pozharov [Toxic components of fires]. Sankt-Peterburg. 2008. 208 p. (In Russ.)

12. Mogilenkova L.A., Rembovskiy V.R. Rol’ geneticheskogo polimorfizma i razlichiya v detoksikatsii khimicheskikh veshchestv v organizme cheloveka [Role of genetic polymorphism and differences in the detoxification of chemical substances in the human body]. Gigiena i sanitariya [Hygiene & Sanitation]. 2016. Vol. 95, N 3. Pp. 255–262. DOI: 10.18821/0016-99002016-95-3-255-262. (In Russ.)

13. Pyrerko L.V. Vozdeistvie dioksinov na zdorov’e cheloveka [The effect of dioxins on human health]. Aktual’nye nauchnye issledovaniya v sovremennom mire [Recent research in the modern world] : Scientific. Conf. Proceedings. Ed. A.I. Vostretsov. Neftekamsk. 2018. Pp. 22–25. (In Russ.)

14. Rumak V.S., Umnova N.V., Sofronov G.A. Molekulyarnye i kletochnye aspekty toksichnosti dioksinov [Molecular and Cellular Aspects of Dioxin Toxicity]. Vestnik Rossiiskoi akademii meditsinskikh nauk [Annals of the Russian Academy of Medical Sciences]. 2014. Vol. 69, N 3-4. Pp. 77–84. DOI: 10.15690/vramn.v69.i3-4.1000. (In Russ.)

15. Strel’tsova I.V., Skutova A.V. Meditsinskie aspekty professional’noi deyatel’nosti pozharnykh [Medical aspects of the professional activities of firefighters]. Nauchnyi zhurnal [Scientific magazine]. 2017. N 5. Pp. 105–106. (In Russ.)

16. Khisamova Z.Zh. Dioksiny i dioksinopodobnye soedineniya [Dioxins and dioxin-like compounds]. Nauka i innovatsii v APK XXI veka [Science and Innovation in the AIC of the 21st Century] : Scientific. Conf. Proceedings. Kazan’. 2018. Pp. 454– 456. (In Russ.)

17. Khrunin A.V., Khokhrin D.V., Limborska S.A. Glutathione-S-transferase gene polymorphism in Russian populations of European part of Russia. Russian Journal of Genetics. 2008. Vol. 44, N 10. Pp. 1241–1245.

18. Tchernyak Yu.I., Grassman D.A. Vozdeistvie dioksinov na pozharnykh [Influence of dioxines on firemen]. Meditsina truda i promyshlennaya ekologiya [Occupational medicine and industrial ecology]. 2007. N 6. Pp. 18–21. (In Russ.)

19. Chernyak Yu.I., Grassman D.A., Kolesnikov S.I. Vliyanie stoikikh organicheskikh zagryaznitelei na biotransformatsiyu ksenobiotikov [The effect of persistent organic pollutants on the biotransformation of xenobiotics]. Novosibirsk. 2007. 124 p. (In Russ.)

20. Chernyak Yu.I., Portyanaya N.I., Merinova A.P. [et al.]. Opredelenie enzimaticheskoi aktivnosti tsitokhroma r450 (cyp)1a2 u «shelekhovskikh» pozharnykh [Determination of the enzymatic activity of cytochrome p450 (cyp) 1a2 in “shelekhovskie” firefighters]. Toksikologicheskii vestnik [Toxicological review]. 2002. N 2. Pp. 5–10. (In Russ.)

21. Chernyak Y.I., Shelepchikov A.A., Grassman J.A. Modifikatsiya dioksin-signal’nogo puti u vysokoeksponirovannykh pozharnykh [Modification of the dioxin signaling pathway in highly exposed firefighters]. Byulleten’ Vostochno-Sibirskogo nauchnogo tsentra Sibirskogo otdeleniya Rossiiskoi akademii meditsinskikh nauk [Bulletin of Eastern-Siberian Scientific Center of Siberian Branch of Russian Academy of Medical Sciences]. 2007. N 2. Pp. 65–71. (In Russ.)

22. Shelepchikov A.A., Chernyak Yu.I., Brodskii E.S., Feshin D.B., Grassman D.A. Polikhlorirovannye dibenzo-p-dioksiny, dibenzofurany i bifenily v syvorotke krovi pozharnykh irkutskogo regiona [Polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls in blood serum of firefighters of Irkutsk oblas]. Sibirskii meditsinskii zhurnal [Siberian Medical Journal]. 2012. Vol. 110, N 3. Pp. 53–59. (In Russ.)

23. Gao L-Y., Hao X-L., Zhang L. [et al.]. Identification and characterization of differentially expressed lncRNA in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate. Human & Experimental Toxicology. 2020. Vol. 39, N 5. Pp. 748–761. DOI: 10.1177/0960327119899996.

24. Gilliland F.D., Li Y.-F., Saxon A. [et al.]. Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study. Lancet. 2004. Vol. 363, N 9403. Pp. 119– 125. DOI: 10.1016/S0140-6736(03)15262-2.

25. Hung R.J., Boffetta P., Brockmöller J. [et al.]. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis. Carcinogenesis. 2003. Vol. 24, N 5. Pp. 875–882. DOI: 10.1093/carcin/bgg026.

26. Johanson H., Hyland V., Wicking C. [et al.]. DNA elution from buccal cells stored on Whatman FTA Classic Cards using a modified methanol fixation method. Botechniques. 2009. Vol. 46, N 4. Pp. 309–311. DOI: 10.2144/000113077.

27. Masetti S., Botto N., Manfredi S. [et al.]. Interactive effect of the glutathione S-transferase genes and cigarette smoking on occurrence and severity of coronary artery risk. J. Mol. Med. 2003. Vol. 81, N 8. Pp. 488–494. DOI: 10.1007/s00109003-0448-5.

28. Palmer C.N., Doney A.S., Lee S.P. [et al.]. Glutathione S-transferase M1 and P1 genotype, passive smoking, and peak expiratory flow in asthma. Pediatrics. 2006. Vol. 118, N 2. Pp. 710–716. DOI: 10.1542/peds.2005-3030.

29. Pavanello S., Clonfero E. Biological indicators of genotoxic risk and metabolic polymorphisms. Mutat. Res. 2000. Vol. 463, N 3. Pp. 285–308. DOI: 10.1016/s1383-5742(00)00051-x.

30. Phillips K.A., Veenstra D.L., Oren E. [et al.]. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001. Vol. 286, N 18. Pp. 2270–2279. DOI: 10.1001/jama.286.18.2270.

31. Rotunno M., Yu K., Lubin J.H. [et al.]. Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression. PLoS One. 2009. Vol. 4, N 5. Pp. e5652. DOI: 10.1371/journal.pone.0005652.

32. Sarmanov J., Benesov K., Gut I. [et al.]. Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin’s and non-Hodgkin’s lymphomas. Hum. Mol. Genet. 2001. Vol. 10, N 12. Pp. 1265–1273. DOI: 10.1093/hmg/10.12.1265.

33. Shin A., Kang D., Choi J.Y. [et al.]. Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women. Exp. Mol. Med. 2007. Vol. 39, N 3. Pp. 361–366. DOI: 10.1038/emm.2007.40.

34. Siraj A.K., Ibrahim M., Al-Rasheed M. [et al.]. Polymorphisms of selected xenobiotic genes contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population // BMC Med. Genet. 2008. Vol. 5. Pp. 9–61. DOI: 10.1186/1471-2350-9-61.

35. Wang X., Zuckerman B., Pearson C. [et al.]. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA. 2002. Vol. 287, N 2. Pp. 195–202. DOI: 10.1001/jama.287.2.195.

36. Wright C.M., Larsen J.E., Colosimo M.L. [et al.]. Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in nonsmall cell lung cancer. Eur. Respir J. 2010. Vol. 35, N 1. Pp. 152–159. DOI: 10.1183/09031936.00120808.