Matthews J B, Adomat H, Skov K A
BC Cancer Research Centre, Vancouver, Canada.
Anticancer Drugs. 1993 Aug;4(4):463-70. doi: 10.1097/00001813-199308000-00007.
The literature contains conflicting evidence regarding the hypoxic toxicity of cisplatin. We have found that in Chinese hamster ovary cells, cisplatin was up to 2.6 times more effective at reducing survival to 2% in hypoxic, compared with aerobic cells. Furthermore, using atomic absorption spectroscopy, it was determined that cells treated in hypoxia showed consistently higher accumulation (up to 1.5 times) and DNA binding (up to 1.7 times) than aerobic cells. Hypoxic cells also showed greater toxicity per platinum-DNA adduct than those treated in air, suggesting that increased binding of the drug, alone, cannot account for its increased hypoxic cytotoxicity. We suggest that the hypoxia selectivity of cisplatin involves several different mechanisms and possible explanations for these results are discussed.
关于顺铂的缺氧毒性，文献中存在相互矛盾的证据。我们发现，在中国仓鼠卵巢细胞中，与需氧细胞相比，顺铂在缺氧条件下将细胞存活率降低至2%的效果高达2.6倍。此外，使用原子吸收光谱法测定发现，缺氧处理的细胞比需氧细胞表现出持续更高的蓄积（高达1.5倍）和DNA结合（高达1.7倍）。缺氧细胞也比在空气中处理的细胞表现出更高的每个铂-DNA加合物毒性，这表明仅药物结合增加并不能解释其缺氧细胞毒性的增加。我们认为顺铂的缺氧选择性涉及几种不同机制，并对这些结果的可能解释进行了讨论。
