Wilson R E, Keng P C, Sutherland R M
University of Rochester Cancer Center, NY 14642.
J Natl Cancer Inst. 1989 Aug 16;81(16):1235-40. doi: 10.1093/jnci/81.16.1235.
Chinese hamster ovary cells exposed to hypoxia developed an 80-fold resistance to a subsequent 1-hour exposure to doxorubicin (ADR) in air. Recovery in air before drug exposure resulted in loss of resistance. Cells exposed to hypoxia for 20 hours followed by a 15-hour recovery were still twofold to threefold more resistant than aerobic cells to a short pulse of ADR. A subpopulation of cells was generated that was at least twice as large as aerobic cells and contained greater than normal G2-M DNA content. This subpopulation showed no resistance to a continuous exposure to either ADR or methotrexate, nor was it more resistant to a pulse of ADR than the remaining cells with normal DNA content. Our data indicate that hypoxia can produce significant ADR resistance. However, conditions resulting in overproduced DNA did not cause significant additional resistance.
暴露于低氧环境的中国仓鼠卵巢细胞对随后在空气中1小时的阿霉素（ADR）暴露产生了80倍的抗性。在药物暴露前在空气中恢复导致抗性丧失。暴露于低氧环境20小时后再恢复15小时的细胞，与需氧细胞相比，对短脉冲ADR的抗性仍高2至3倍。产生了一个细胞亚群，其大小至少是需氧细胞的两倍，且G2-M期DNA含量高于正常水平。该亚群对持续暴露于ADR或甲氨蝶呤均无抗性，对ADR脉冲的抗性也不比其余DNA含量正常的细胞更高。我们的数据表明，低氧可产生显著的ADR抗性。然而，导致DNA过量产生的条件并未引起显著的额外抗性。
