Born R, Eichholtz-Wirth H
Br J Cancer. 1981 Aug;44(2):241-6. doi: 10.1038/bjc.1981.175.
Chronically hypoxic cells were 5 times more resistant to Adriamycin (ADR) than exponentially growing oxic cells. On reoxygenation, resistance decreased slowly to reach the ADR sensitivity of oxic cells after 24 h. With increasing pH, ADR efficiency increased more in oxic than in chronically hypoxic cells. With increasing cell density, ADR efficiency decreased linearly. The differences in ADR efficiency under the various conditions were accompanied by differences in intracellular ADR uptake. Chronically hypoxic cells incorporated 1.6 times less than oxic cells; the incorporation rate at pH 6.5 was half that at pH 7.4; and at a cell density of 5 X 10(5)/bottle the intracellular uptake was 6 times that at 5 X 10(6)/bottle. The observed differences in uptake of ADR were not, however, sufficient to explain the differences in cytotoxicity.
长期缺氧细胞对阿霉素(ADR)的耐药性是指数生长的有氧细胞的5倍。复氧后,耐药性缓慢下降,24小时后达到有氧细胞的ADR敏感性。随着pH值升高,ADR在有氧细胞中的效率比长期缺氧细胞增加得更多。随着细胞密度增加,ADR效率呈线性下降。不同条件下ADR效率的差异伴随着细胞内ADR摄取的差异。长期缺氧细胞的摄取量比有氧细胞少1.6倍;pH 6.5时的摄取率是pH 7.4时的一半;细胞密度为5×10⁵/瓶时,细胞内摄取量是5×10⁶/瓶时的6倍。然而,观察到的ADR摄取差异不足以解释细胞毒性的差异。