Universität Ulm, Institut für Humangenetik, 89069 Ulm, Germany.
Mutat Res. 2013 Jul-Aug;747-748:1-5. doi: 10.1016/j.mrfmmm.2013.04.008. Epub 2013 May 2.
Genotoxic effects of hyperthermia in vitro and in vivo have repeatedly been reported. Short-duration heat shocks and elevated temperature over longer time periods have been shown to induce DNA damage, chromosomal damage and to inhibit DNA repair. Using the comet assay and the micronucleus test, we now investigated temperature- and time-related effects on DNA damage and chromosomal effects of hyperthermia on the A549 human lung cell line. We also related the genotoxic effects to cytotoxic effects and the induction of apoptosis. Our results indicate that exposure to hyperthermia (42-48°C for 30-120min) induced genotoxic effects in a temperature- and time-related manner. Interestingly, hyperthermia-induced DNA damage measured by the comet assay was not rapidly removed by post-incubation at 37°C but even increased after exposure to 48°C for 60min. Cytotoxic effects occurred in parallel to the genotoxic effects but apoptosis was not significantly induced under these experimental conditions.
体外和体内研究均表明高热具有遗传毒性。短时间热休克和长时间高温均会导致 DNA 损伤、染色体损伤,并抑制 DNA 修复。本研究采用彗星实验和微核实验,检测了热疗对 A549 人肺细胞系的 DNA 损伤和染色体损伤的温度和时间相关性,并将遗传毒性与细胞毒性和细胞凋亡的诱导相关联。结果表明,热疗(42-48°C,30-120min)会导致与温度和时间相关的遗传毒性。有趣的是,彗星实验检测到的热疗诱导的 DNA 损伤在 37°C 孵育时并未迅速消除,而在 48°C 孵育 60min 后甚至增加。细胞毒性与遗传毒性平行发生,但在这些实验条件下,细胞凋亡并未显著诱导。