Naito K, He Q, Skog S, Tribukait B, Andersson L, Hisazumi H
Department of Medical Radiobiology, Karolinska Institute, Stockholm, Sweden.
Int J Hyperthermia. 1989 May-Jun;5(3):329-40. doi: 10.3109/02656738909140459.
Inhibition of the salvage DNA synthesis was studied in ascites tumour cells up to 240 min at moderately increased temperatures of 39 degrees C, 40.5 degrees C and 43 degrees C alone or in combination with adriamycin (ADR). Hyperthermia and ADR acted additively on salvage DNA synthesis. The [3H]thymidine (TdR) incorporation was strongly related to the cellular uptake of [3H]TdR. In order to evaluate the significance of the decrease in [3H]TdR uptake for the incorporation into DNA, the thymidine kinase (TK) has also been studied. TK activity started to decrease at a temperature of 39 degrees C, probably due to inhibition of translation and/or transcription of the enzyme, and was almost completely inhibited at 43 degrees C. ADR did not affect TK activity. Inhibition of DNA synthesis by aphidicolin neither decreased the ability of the cell to take up [3H]TdR nor the ability to affect TK activity. We concluded that moderate increases in temperature alone, or in combination with ADR, inhibit salvage DNA synthesis by inhibition of TdR uptake, possibly due to inhibition of phosphorylation; ADR, on the contrary, inhibits TdR uptake by other mechanisms such as changes in membrane function.
在39℃、40.5℃和43℃等适度升高的温度下，单独或与阿霉素（ADR）联合使用，在腹水肿瘤细胞中研究了补救性DNA合成的抑制情况，持续时间长达240分钟。热疗和阿霉素对补救性DNA合成起相加作用。[3H]胸苷（TdR）掺入与[3H]TdR的细胞摄取密切相关。为了评估[3H]TdR摄取减少对其掺入DNA的意义，还研究了胸苷激酶（TK）。TK活性在39℃时开始下降，可能是由于该酶的翻译和/或转录受到抑制，在43℃时几乎完全被抑制。阿霉素不影响TK活性。放线菌素D对DNA合成的抑制既不降低细胞摄取[3H]TdR的能力，也不影响其影响TK活性的能力。我们得出结论，单独适度升高温度或与阿霉素联合使用，可能通过抑制磷酸化而抑制TdR摄取，从而抑制补救性DNA合成；相反，阿霉素通过其他机制如膜功能改变来抑制TdR摄取。
