Krishnan D, Singh D R, Madhvanath U
Br J Cancer. 1978 Jun;37(6):1026-32. doi: 10.1038/bjc.1978.149.
This paper discusses the results of experiments using γ-rays and a hypoxic sensitizer metronidazole (MET) and also a well-known protector, mercaptoethylamine (MEA), individually and in combination, on the survival of the yeast S. cerevisiae BZ 34. MET (5mM) gave a hypoxic enhancement ratio (ER) of 1·3. MEA (5mM, 10mM) gave a dose-modifying factor (DMF) of 1·9 and 2·3 respectively for euoxic cells. However, the DMFs for hypoxic cells were 1·0 and 1·1 for 5 and 10mM concentrations of MEA. A combination of 5mM MEA and 5mM MET gave a DMF of 2·0 for euoxic cells and the ER remained at 1·3 for hypoxic cells. The "effective" oxygen enhancement ratios were 2·3 and 1·7 for the control and the sensitizer respectively. In the combination this value was equal to or even slightly less than 1. All DMF, ER and OER values were derived from D(0) values of the survival curves. The values based on 10% survival are almost equal to those derived from D(0) values. All the survival curves gave the same extrapolation number, showing that the chemicals individually or in combination were truly dose-modifying.These results indicate that protectors such as MEA could be preferentially protecting euoxic cells, and that combining such "oxic protectors" with a hypoxic sensitizer could result in protecting euoxic cells while the sensitization of hypoxic cells was not much reduced. The implications of our results for radiotherapy are discussed. It appears that the use of nontoxic oxic protectors may be a useful adjuvant in overcoming the hypoxic-cell problem in radiotherapy.
本文讨论了使用γ射线、低氧增敏剂甲硝唑（MET）以及一种著名的防护剂巯基乙胺（MEA）单独或联合作用于酿酒酵母BZ 34的存活情况的实验结果。MET（5mM）的低氧增强比（ER）为1.3。MEA（5mM、10mM）对需氧细胞的剂量修正因子（DMF）分别为1.9和2.3。然而，对于低氧细胞，5mM和10mM浓度的MEA的DMF分别为1.0和1.1。5mM MEA与5mM MET联合使用时，对需氧细胞的DMF为2.0，对低氧细胞的ER仍为1.3。对照和增敏剂的“有效”氧增强比分别为2.3和1.7。在联合使用时，该值等于或甚至略小于1。所有的DMF、ER和OER值均来自存活曲线的D(0)值。基于10%存活的数值几乎与从D(0)值得出的数值相等。所有存活曲线的外推数相同，表明这些化学物质单独或联合使用时确实具有剂量修正作用。这些结果表明，诸如MEA之类的防护剂可能优先保护需氧细胞，并且将这种“需氧防护剂”与低氧增敏剂联合使用可能在保护需氧细胞的同时，低氧细胞的增敏作用不会大幅降低。文中讨论了我们的结果对放射治疗的意义。看来使用无毒的需氧防护剂可能是克服放射治疗中低氧细胞问题的一种有用辅助手段。
