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- W2134313802 abstract "Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. (1) Hyperthermia: water-submerged heating treatment at both 42 and 44°C for 30 min; (2) Gene amplification assay using PALA* selection of cad¶ gene amplified cells; (3) Southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) γH2AX immunostaining to detect γH2AX foci as an indication for DNA double strand breaks. (1) Heat exposure at both 42 and 44 °C for 30 minutes induces gene amplification. The frequency of cad gene amplification increased by 2.1 and 6.5 folds respectively; (2) Heat exposure at both 42 and 44 °C for 30 minutes induces DNA double strand breaks in HCT116 cells as shown by γH2AX immunostaining. This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and telomere functions are denatured. To our knowledge, this is the first study to provide direct evidence of hyperthermia induced gene amplification. *PALA: N-(phosphoacetyl)-L-aspartate ¶Cad: the cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene." @default.
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- W2134313802 date "2011-10-01" @default.
- W2134313802 modified "2023-10-06" @default.
- W2134313802 title "42 and 44°C Hyperthermia Induces Gene Amplification in Colorectal Cancer HCT116 Cells" @default.
- W2134313802 doi "https://doi.org/10.1016/j.ijrobp.2011.06.1340" @default.
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