Адаптивные реакции фибробластов легких эмбриона человека на производное фуллерена, модифицированного остатками 3-бензотиенилаланина

   Исследовано влияние производного фуллерена с пятью присоединенными остатками 3-бензотиенилаланина и одним атомом водорода (Ф1) на функционирование фибробластов легких эмбриона человека (ФЛЭЧ). Показали, что Ф1 в течение 24 часов проникает в цитоплазму большинства клеток в популяции. Для исследования воздействия Ф1 на ФЛЭЧ выбраны две концентрации: 18,3 нг/мл, входящая в диапазон нетоксичных концентраций, и концентрация, близкая к повреждающей – 28 µг/мл, и три времени инкубации клеток с соединениями – 1, 3 и 24 часа. Обнаружили, что через 24 часа в присутствии низких концентраций Ф1 снижается уровень активных форм кислорода (АФК) в клетках, что обусловлено повышением экспрессии гена NRF2 и увеличением его функциональной активности. Соединение Ф1 в концентрации, близкой к токсичной, вызывает в культивируемых ФЛЭЧ повышение уровня экспрессии гена и белка NOX4, что приводит к синтезу АФК в клетках, к окислительным модификациям и двунитевым разрывам ДНК ядер клеток через 24 часа инкубации. Не обнаружено влияния Ф1 на уровень экспрессии гена и белка BRCA1 что, вероятно, способствует образованию в клетках и поддержанию на высоком уровне двунитевых разрывов ДНК через 24 часа инкубации. Повышение экспрессии антиапоптотических генов в ФЛЭЧ через 24 часа культивирования с Ф1 может способствовать выживанию клеток с поврежденной ДНК.

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