Теоретическая и прикладная экология1995-43012618-840610.25750/1995-4301-2026-1-177-188OtherОценка наследственной компоненты фторной экотоксической нагрузкиAssessment of the hereditary component of fluoride ecotoxic loadСтариченкоВ. И.StarichenkoV. I.starichenko@ipae.uran.ruhttps://orcid.org/0000-0001-9744-916XInstitute of Plants and Animal Ecology UB RASYekaterinburgRussiaУральского отделения РАНЕкатеринбургРоссия250320261177188http://www.envjournal.ru/ari/v2026/v1/26119.pdf

Фтор – один из наиболее токсичных и широко распространённых промышленных загрязнителей природной среды. В экологических проблемах фторного загрязнения выявление наследственной компоненты его накопления играет особую роль как способствующей поддержанию его уровня в ряду поколений. Однако факторы индивидуальной изменчивости аккумуляции фтора у млекопитающих, в частности, наследственная составляющая вариабельности накопления, не выявлены. Это обусловлено методологическими особенностями исследования параметров депонирования фтора, недоступных для изучения в прямых экологических наблюдениях. Экспериментальное исследование на лабораторных мышах позволяет оценить величину наследственной компоненты депонирования фтора. Исследовали накопление фтора у потомства трёх линий инбредных мышей (внутрилинейная корреляция) в фоновых условиях и после хронического поступления токсиканта. Использовался также вариант семейного анализа (внутрисемейная корреляция). Это классический подход к оценке наследственной изменчивости количественных признаков. Самки получали фтор с пищей в течение всего периода беременности и до 1,5-мес. возраста потомства. При оценке учитывали эффект влияния пола животных и величины помёта в семье. Аккумуляция фтора у отдельных индивидов различалась в некоторых экспериментальных группах в 3–6,5 раз. В то же время особенности депонирования фтора оказались характерными для целых семейств. Общая наследственная составляющая (внутрилинейная и внутрисемейная) кумуляции фтора сопоставима с наследственной корреляцией морфологических признаков, имеющих высокую наследственную детерминацию развития (R = 0,50–0,56, p < 0,0001 и R = 0,45–0,53–0,58, p < 0,0001 соответственно). В зависимости от варианта анализа (вся выборка или только опытная группа), семейная составляющая изменчивости сопоставима или значительно выше (в 2–3 раза) эффекта линейной принадлежности животных. Для фоновых уровней фтора наследственная обусловленность его депонирования статистически незначима. Полученные результаты могут быть экстраполированы на полевых грызунов.

Fluoride is one of the most toxic and widely spread industrial pollutants of the environment. Identifying the hereditary component of fluoride accumulation plays a special role in environmental issues of fluoride pollution, as contributing to maintaining its level across generations. However, the factors of individual variability of fluoride accumulation in mammals, in particular, the hereditary component of accumulation variability, have not been identified. This is due to the methodological features of studying fluoride deposition parameters that are inaccessible in direct environmental observations. An experimental study on laboratory mice allows us to estimate the magnitude of the hereditary component of fluoride deposition. The fluoride accumulation was studied in the progeny of three strains of inbred mice (intrastrain correlation) against the background conditions and following chronic intake of the toxicant. The variant of the family analysis (intrafamily correlation) was also used. It is a classical approach to the hereditary variation of quantitative traits assessment. Fluoride entered the female mice body with food during the whole gestation period and up to the age of 1.5 month of the progeny. The assessment was performed with the control of the animal sex and litter size effect. Individual parameters of fluoride accumulation differed in certain experimental groups by 3–6.5 times. At the same time the specifics of fluoride accumulation was typical of the entire families. Combined hereditary component (intrastrain and intrafamily) of the fluoride accumulation was comparable with the hereditary correlation of morphological characteristics with known hereditary dependence of development (R = 0.50–0.56, p < 0.0001 and R = 0.45–0.53–0.58, p < 0.0001 respectively). Notably, the family component of the variability depending on the analysis option (the entire sample or just the experimental group) is comparable and exceeds the animal’s strain effect by 2–3 times. For background fluoride level the hereditary dependence of its deposition is statistically insignificant. The results obtained can be extrapolated to field rodents.

familial analysisenvironmental toxicologyfluoridebone tissueinbred mouse strainsANOVAintraclass correlation coefficientэкологическая токсикологияфторкостная тканьлинейные мышидисперсионный анализкоэффициент внутриклассовой корреляцииметод семейного анализаThis study was performed within the frameworks of state contract of the Institute of Plant and Animal Ecology, Ural Branch, Russian Academy of Sciences (project No. 122021000077–6).1. Faccini J.M. Fluoride and bone // Calcif. Tissue Res. 1969. V. 3. P. 1–16. doi: 10.1007/BF020586412. Knizhnikov V.A. Calcium and fluoride: radiation-hygienic aspects. Moskva: Atomizdat, 1975. 199 p. (in Russian).3. Fluorine and fluorides. Environmental Health Criteria 36. Geneva: WHO, 1984. 100 p.4. Boivin G., Meunier P.J. Fluoride and bone: Toxic effects and therapeutic role // Therapeutic uses of trace elements / Eds. J. Nève, P. Chappuis, M. Lamand. Boston, MA: Springer, 1996. P. 283–295. doi: 10.1007/978-1-4899-0167-5_495. Lyubashevskiy N.M., Tokar V.I., Shcherbakov S.V. Technogenic environmental pollution by fluoride (ecological and medical-social aspects). Yekaterinburg: Ural Branch of the RAS, 1996. 239 p. (in Russian).6. Whitford G.M. The metabolism and toxicity of fluoride // Monogr. Oral Sci. 1996. V. 16. 156 p. doi: 10.1159/isbn.978-3-318-04022-77. Toxicological profile for fluorides, hydrogen fluoride, and fluorine. Atlanta, GA: Agency for Toxic Substances and Disease Registry (US), 2003. 404 p.8. Mousny M., Banse X., Wise L., Everett E.T., Hancock R., Vieth R., Devogelaer J.P., Grynpas M.D. The genetic influence on bone susceptibility to fluoride // Bone. 2006. V. 39. No. 6. P. 1283–1289. doi: 10.1016/j.bone.2006.06.0069. Yanin E.P. Fluoride in the environment: (prevalence, behavior, technogenic pollution) // Ecological expertise. 2007. No. 4. P. 2–98 (in Russian).10. Gornostaeva E.A., Fuks S.L. The effect of fluorinated compounds on living organisms (review) // Theoretical and Applied Ecology. 2017. No. 1. P. 14–24 (in Russian). doi: 10.25750/1995-4301-2017-1-014-02411. WHO. The public health impact of chemicals: knowns and unknowns WHO. International Programme on Chemical Safety. Geneva, 2016. 16 p.12. Mogilenkova L.A., Rembovskiy V.R. Role of genetic polymorphism and differences in the detoxification of chemical substances in the human body // Hygiene & Sanitation. 2016. V. 95. No. 3. P. 255–262 (in Russian). doi: 10.18821/0016-9900-2016-95-3-255-26213. Polzik E.V., Valova G.A., Zinger V.E., Sysoeva L.A. Some problems of biomedical prophylaxis occupational fluorosis // Occupational medicine and industrial ecology. 1995. V. 5. P. 44–47 (in Russian).14. Lavryashina M.B., Ul’ianova M.V., Druzhinin V.G., Tolochko T.A. A study of the genetic basis of susceptibility to occupational fluorosis in aluminum industry workers of Siberia // Russ. J. Genet. 2003. V. 39. No. 7. P. 823–827.15. Bol’shakov V.N., Vasil’ev A.G., Vasil’eva I.A., Gorodilova Yu.V., Kolcheva N.E., Lyubashevskii N.M., Chibiryak M.B. Technogenic morphological variation of the pygmy wood mouse (Sylvaemus uralensis Pall.) in the Urals // Russ. J. Ecol. 2012. V. 43. No. 6. P. 448–453. doi: 10.1134/S106741361206003316. Lyubashevsky N.M., Emelyanov A.M., Bakhtiyarova M.F., Juraev M.I., Kotomtsev V.V., Mokronosov A.A., Portnaya L.V., Chibiryak M.V., Starichenko V.I. Prospects for animal husbandry in the TADAZ area // Recommendations of the scientific and practical conference on reviewing the status of the results of the implementation of the “Target scientific and technical program of work to reduce emissions of pollutants into the environment by the Tajik Aluminum Plant to maximum permissible levels”. Tursunzade, 1991. P. 84–90 (in Russian).17. Everett E.T., McHenry M.A.K., Reynolds N., Eggertsson H., Sullivan J., Kantmann C., Martinez-Mier E.A., Warrick J.M., Stookey G.K. Dental fluorosis: variability among different inbred mouse strains // J. Dent. Res. 2002. V. 81. No. 11. P. 794–798. doi: 10.1177/081079418. Yan D., Willett T.L., Gu X.M., Martinez-Mier E.A., Sardone L., McShane L., Grynpas M., Everett E.T. Phenotypic variation of fluoride responses between inbred strains of mice // Cells Tissues Organs. 2011. V. 194. No. 2–4. P. 261–267. doi: 10.1159/00032422419. Vogel F., Motulsky A.G. Human genetics: problems and approaches. Berlin, Heidelberg: Springer-Verlag, 2010. 981 p.20. Starichenko V.I. Metabolism of osteotropic toxical substances: hereditary determination // Ecol. Genet. 2010.V. 8. No. 3. P. 27–37 (in Russian).21. Starichenko V.I. Hereditary component of variation in 90Sr deposition in inbred mice under exogenous conditions that affect bone formation // Appl. Radiat. Isot. 2018. V. 140. P. 126–132. doi: 10.1016/j.apradiso.2018.07.00622. Everett E.T. Fluoride’s effects on the formation of teeth and bones, and the influence of genetics // J. Dent. Res. 2011. V. 90. No. 5. P. 552–560. doi: 10.1177/002203451038462623. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. Washington, D.C.: National Academies Press, 2011. 246 p.24. Leary S., Underwood W., Anthony R., Cartner S., Corey D., Grandin T., Greenacre C., Gwaltney-Brant S., McCrackin M., Meyer R., Miller D., Shearer J., Yanong R., Golab G., Patterson-Kane E. AVMA guidelines for the euthanasia of animals: 2013 edition // J. Am. Vet. Med. Assoc. 2013. 102 p.25. Khazemova L.A., Radovskaya T.L., Kruglova N.V., Kachalkova T.K. Fluorine assessment in plant material // Agrokhimiya. 1983. No. 6. P. 66–72 (in Russian).26. Mather K., Jinks J.L. Introduction to biometrical genetics. London: Chapman and Hall Ltd., 1982. 238 p.27. Falconer D.S., Mackay T.F.C. Introduction to quantitative genetics. Essex: Longman House, 1996. 448 p.28. Beamer W.G., Donahue L.R., Rosen C.J., Baylink D.J. Genetic variability in adult bone density among inbred strains of mice // Bone. 1996. V. 18. No. 5. P. 397–403. doi: 10.1016/8756-3282(96)00047-629. Slemenda C.W., Turner C.H., Peacock M., Christian J.C., Sorbel J., Hui S.L., Johnston C.C. The genetics of proximal femur geometry, distribution of bone mass and bone mineral density // Osteoporos. Int. 1996. V. 6. No. 2. P. 178–182. doi: 10.1007/BF0162394430. Scheffé H. The analysis of variance. New York: Wiley, 1959. 496 p.31. Sokal R.R., Rohlf F.J. Biometry: the principles and practice of statistics in biological research. New York: W.H. Freeman & Co., 1995. 887 p.32. Gabovich R.D. Fluoride and its hygienic value. Moscow: Medgiz, 1957. 250 p. (in Russian).33. ICRP Publication 20. Alkaline earth metabolism in adult man. Oxford: Pergamon Press, 1973. 99 p.34. Hefti A., Marthaler T.M. Bone fluoride concentrations after 16 years of drinking water fluoridation // Caries Res. 1981. V. 15. No. 1. P. 85–89. doi: 10.1159/00026050435. Il’enko A.I., Krapivko T.P. Animal ecology in the radiation biogeocoenose. Moskva: Nauka, 1989. 224 p. (in Russian).36. Shagina N.B., Tolstykh E.I., Degteva M.O. Improvements in the biokinetic model for strontium with allowance for age and gender differences in bone mineral metabolism // Radiat. Prot. Dosimetry. 2003. V. 105. No. 1-4. P. 619–622. doi: 10.1093/oxfordjournals.rpd.a00631437. Fluoride concentrations in human bones // Nutr. Rev. 1959. V. 17. No. 5. P. 133–136. doi: 10.1111/j.1753-4887.1959.tb06433.x38. Pharmacology of fluorides / Ed. F.A. Smith // Handbuch der experimentellen Pharmakologie. V. 20. Pt. 2. Berlin, Heidelberg, New York: Springer; Verlag, 1966. 452 p. doi: 10.1007/978-3-642-99973-439. Carvalho J.G., Leite A.L., Yan D., Everett E.T., Whitford I G.M., Buzalaf M.A.R. Influence of genetic background on fluoride metabolism in mice // J. Dent. Res. 2009. V. 88. No. 11. P. 1054–1058. doi: 10.1177/002203450934724940. Vasil’ev A.G. Epigenetic bases of phenetics: towards population meronomy. Ekaterinburg: Akademkniga, 2005. 640 p. (in Russian).41. Casellas J. Inbred mouse strains and genetic stability: a review // Animal. 2011. V. 5. No. 1. P. 1–7. doi: 10.1017/S175173111000166742. Chebib J., Jackson B.C., López-Cortegano E., Tautz D., Keightley P.D. Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site // Heredity. 2021. V. 126. No. 1. P. 107–116. doi: 10.1038/s41437-020-00361-143. Lyubashevsky N.M., Starichenko V.I. Lactation and the phenomenon of biodiversity (epigenetics of the mineral metabolism of rodents) // Genetics of Populations: Progress and Perspectives: Proceedings of the International Conference commemorating the 80th birthday of Academician Y.P. Altukhov. Zvenigorod, April 17–21, 2017. Moskva, 2017. P. 152–154 (in Russian).44. Kitsiou-Tzeli S., Tzetis M. Maternal epigenetics and fetal and neonatal growth // Curr. Opin. Endocrinol. Diabetes Obes. 2017. V. 24. No. 1. P. 43–46. doi: 10.1097/MED.000000000000030545. Ge Z.J., Sun Q.Y. Maternal epigenetic inheritance // Transgenerational Epigenetics. 2019. V. 13. P. 75–105. doi: 10.1016/B978-0-12-816363-4.00005-546. Goldman M., Della Rosa R.J. Studies of the dynamics of strontium metabolism under conditions of continual ingestion to maturity // Strontium metabolism: proceedings of an International symposium on some aspects of strontium metabolism / Eds. J.M.A. Lenihan, J.F. Loutit, J., G. Martin. London, New York: Academic Press, 1967. P. 181–194.47. Jang H., Serra C. Nutrition, epigenetics, and diseases // Clin. Nutr. Res. 2014. V. 3. No. 1. P. 1–8. doi: 10.7762/cnr.2014.3.1.148. Murdoch B.M., Murdoch G.K., Greenwood S., McKay S. Nutritional influence on epigenetic marks and effect on livestock production // Front. Genet. 2016. V. 7. Article No. 182. doi: 10.3389/fgene.2016.0018249. Starichenko V.I. Accumulation of 90Sr in the bone tissue of northern mole voles in the head portion of the East Ural Radioactive Trace // Russ. J. Ecol. 2011. V. 42. No. 1. P. 64–70. doi: 10.1134/S1067413611010115

The author is grateful to I.A. Kshnyasev for his help in the statistical data processing and to N.M. Lyubashevsky – for fruitful discussion of the results.