O'Hara J A, Douple E B, Abrams M J, Picker D J, Giandomenico C M, Vollano J F
Dartmouth-Hitchcock Medical Center, Hanover, NH 03756.
Int J Radiat Oncol Biol Phys. 1989 Apr;16(4):1049-52. doi: 10.1016/0360-3016(89)90913-9.
The effects of the combination of several meso-substituted, water soluble metalloporphyrins with ionizing radiation on hypoxic and oxic monolayers of Chinese hamster fibroblast (V79N) cells were studied. The metalloporphyrins tested included a series of cationic metalloporphyrins complexed with Co(III), Zn(II), Fe(III), Cu(II), Pd(II) or Mn(III) and a series of anionic porphyrins chelated with Co(III), Fe(III), Cu(II), Rh(III), Mn(III) or Sn(IV). Both cationic and anionic free porphyrins were also tested. Cationic ligands were tetrakis(4N-methylpyridyl)porphine [TMPyP], tetrakis(4N-trimethylamino phenyl)porphine [TMAP], tetrakis(4N-butylpyridyl)porphine [TBPyP] and tetrakis(3N-methylpyridyl)porphine [3TMPyP]. Anionic ligands tested were tetrakis(4-sulfonato phenyl)porphine [TPPS], tetrakis(biphenyl)porphine sulfonate [TBPS] and tetrakis(4-carboxyphenyl)porphine [TCPP]. SER calculated from survival curves and SFR from one radiation dose were used to assess the relative effectiveness of this class as non-cytotoxic hypoxic and oxic cell-kill potentiators. Comparisons were made at 100 microM, which was essentially non-toxic (greater than 70% survival) for all porphyrins tested except for Co[TMPyP] (approximately 50% survival after 1 hour at 37 degrees C under oxic conditions). The greatest effects on radiation-induced cell kill were achieved with Co[TPPS] and Co[TMPyP] with SER values of 2.3 and 2.4 respectively. Porphyrin analogs with no coordinated metal were found to be less active than the same compound with metal. The overall charge on the molecule did not systematically relate to the biological activity of the compounds tested.
研究了几种中取代的水溶性金属卟啉与电离辐射联合作用对中国仓鼠成纤维细胞（V79N）缺氧和有氧单层细胞的影响。所测试的金属卟啉包括一系列与Co(III)、Zn(II)、Fe(III)、Cu(II)、Pd(II)或Mn(III)络合的阳离子金属卟啉，以及一系列与Co(III)、Fe(III)、Cu(II)、Rh(III)、Mn(III)或Sn(IV)螯合的阴离子卟啉。还测试了阳离子和阴离子游离卟啉。阳离子配体为四（4-N-甲基吡啶基）卟啉[TMPyP]、四（4-N-三甲基氨基苯基）卟啉[TMAP]、四（4-N-丁基吡啶基）卟啉[TBPyP]和四（3-N-甲基吡啶基）卟啉[3TMPyP]。所测试的阴离子配体为四（4-磺基苯基）卟啉[TPPS]、四（联苯基）卟啉磺酸盐[TBPS]和四（4-羧基苯基）卟啉[TCPP]。根据存活曲线计算的SER和一个辐射剂量下的SFR用于评估此类作为无细胞毒性的缺氧和有氧细胞杀伤增强剂的相对有效性。在100 microM下进行比较，除Co[TMPyP]（在37℃有氧条件下1小时后约50%存活）外，该浓度对所有测试卟啉基本无毒（存活率大于70%）。Co[TPPS]和Co[TMPyP]对辐射诱导的细胞杀伤影响最大，SER值分别为2.3和2.4。发现没有配位金属的卟啉类似物比有金属的相同化合物活性低。分子上的总电荷与所测试化合物的生物活性没有系统的关联。
