Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66695610.31857/S0016675824040106cqpqmjГЕНЕТИКА ЧЕЛОВЕКАResearch ArticleLINE-1 methylation index correlates with sister chromatid exchanges and chromatid but not chromosome aberrations in personnel from a nuclear chemical facility with incorporated plutonium-239Индекс метилирования ретротранспозона LINE-1 коррелирует с уровнем сестринских хроматидных обменов и частотой аберраций хроматидного типа у персонала радиохимического производства с инкорпорированным плутонием-239VasilyevS. A.ВасильевС. А.
Russian Federation

Research Institute of Medical Genetics

Научно-исследовательский институт медицинской генетики

stanislav.vasilyev@medgenetics.ruTolmachevaE. N.ТолмачеваЕ. Н.
Russian Federation

Research Institute of Medical Genetics

Научно-исследовательский институт медицинской генетики

stanislav.vasilyev@medgenetics.ruSazhenovaE. A.СаженоваЕ. А.
Russian Federation

Research Institute of Medical Genetics

Научно-исследовательский институт медицинской генетики

stanislav.vasilyev@medgenetics.ruSukhanovaN. N.СухановаН. Н.
Russian Federation

Research Institute of Medical Genetics

Научно-исследовательский институт медицинской генетики

stanislav.vasilyev@medgenetics.ruYakovlevaYu. S.ЯковлеваЮ. С.
Russian Federation

Research Institute of Medical Genetics

Научно-исследовательский институт медицинской генетики

stanislav.vasilyev@medgenetics.ruTorkhovaN. B.ТорховаН. Б.
Russian Federation

Research Institute of Medical Genetics

Научно-исследовательский институт медицинской генетики

stanislav.vasilyev@medgenetics.ruPlaksinM. B.ПлаксинМ. Б.
Russian Federation
stanislav.vasilyev@medgenetics.ruLebedevI. N.ЛебедевИ. Н.
Russian Federation

Research Institute of Medical Genetics

Научно-исследовательский институт медицинской генетики

stanislav.vasilyev@medgenetics.ruTomsk National Research Medical Center of the Russian Academy of SciencesТомский национальный исследовательский медицинский центр Российской академии наукTomsk National Research Medical Center of the Russian Academy of SciencesТомский национальный исследовательский медицинский центр Российской академии наукSiberian State Medical UniversityСибирский государственный медицинский университетSeversk Clinical Hospital, Siberian Federal Clinical Center of the Federal Biomedical AgencyСибирский федеральный научно-клинический центр Федерального медико-биологического агентства1104202460411412226022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/666956

The level of chromosomal abnormalities in the somatic cells of adult individuals is characterized by significant interindividual variability, which may be partly affected by the genetic and epigenetic background. The epigenetic landscape in cells is largely determined by genome methylation. This study aimed to analyse the relationships between global genome methylation and the frequencies of chromosome abnormalities in lymphocytes of plutonium workers. The frequencies of chromosome aberrations, micronuclei, aneuploidy of chromosomes 2, 7, 8, 12, X and Y and sister chromatid exchanges were analysed in the lymphocytes of 40 male workers from a nuclear chemical facility (Seversk, Russia) with incorporated plutonium-239 and 49 healthy male volunteers who had no occupational exposure to ionizing radiation. The long interspersed nuclear elements-1 (LINE-1) methylation index was assessed as a well-known marker of global genome methylation. The frequencies of centromere-negative micronuclei (4.74 ± 2.26‰ vs. 3.02 ± 1.69‰), chromosome-type aberrations (0.81 ± 0.79 vs. 0.44 ± 0.69%) and total chromosome non-disjunction (0.93 ± 0.43 vs. 0.50 ± 0.25%) were significantly higher in the group of workers than in controls (p < 0.05). The LINE-1 methylation index did not differ significantly between the worker and control groups (74.93 ± 3.63 vs. 73.92 ± 4.62%). Correlations between LINE-1 methylation and the frequency of micronuclei (R = –0.35, p = 0.031) were observed in the control group, whereas correlations of LINE-1 methylation with chromatid-type aberrations (R = –0.42, p = 0.012) (but not chromosome-type aberrations) and with sister chromatid exchanges (R = –0.53, p = 0.004) were observed only in the group of plutonium workers. Thus, LINE-1 hypomethylation after plutonium exposure is associated mainly with chromatid breaks, either repaired or misrepaired.

Уровень хромосомных аномалий в соматических клетках взрослых индивидов характеризуется значительной межиндивидуальной изменчивостью, на которую частично могут влиять генетические и эпигенетические факторы. При этом эпигенетический ландшафт в клетках в значительной степени определяется метилированием генома. Цель настоящего исследования – анализ взаимосвязи между глобальным метилированием генома и частотой хромосомных аномалий в лимфоцитах работников, работавших с плутонием. В лимфоцитах 40 мужчин-работников радиохимического предприятия (Северск, Россия) с инкорпорированным плутонием-239 и 49 здоровых мужчин-добровольцев, которые не подвергались профессиональному воздействию ионизирующего излучения, были проанализированы частоты хромосомных аберраций, микроядер, анеуплоидии хромосом 2, 7, 8, 12, X и Y и уровень сестринских хроматидных обменов. Индекс метилирования ретротранспозона LINE-1 был оценен как хорошо известный маркер глобального метилирования генома. В группе работников по сравнению с контролем были достоверно выше частоты центромеро-негативных микроядер (4.74 ± 2.26‰ против 3.02 ± 1.69‰), аберраций хромосомного типа (0.81 ± 0.79 против 0.44 ± 0.69%) и суммарного хромосомного нерасхождения (0.93 ± 0.43 против 0.50 ± 0.25%) (р < 0.05). Индекс метилирования LINE-1 достоверно не отличался между группой работников и контрольной группой (74.93 ± 3.63 против 73.92 ± 4.62%). В контрольной группе наблюдалась корреляция между метилированием LINE-1 и частотой микроядер (R = –0.35, p = 0.031), тогда как в группе работников отмечались корреляции между индексом метилирования LINE-1 и частотой аберраций хроматидного типа (R = –0.42, p = 0.012) (но не аберраций хромосомного типа) и уровнем сестринских хроматидных обменов (R = –0.53, p = 0.004). Таким образом, гипометилирование LINE-1 после воздействия плутония связано главным образом с репарированными или неправильно репарированными разрывами хроматид.

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