Wharen R E, So S, Anderson R E, Laws E R
Neurosurgery. 1986 Oct;19(4):495-501. doi: 10.1227/00006123-198610000-00002.
The parameters of hematoporphyrin-derivative (HpD) photocytotoxicity of human glioma cells in cell culture were studied to determine the optimum wavelength and power density of light, to investigate the influence of tissue oxygenation, and to evaluate the role of singlet oxygen and free radicals in producing cell death. Cell survival curves demonstrated a relative killing efficiency of 12:1 for violet compared to red light. Eighty joules of red light were required to produce 100% cell kill at an HpD concentration of 10 micrograms/ml, a level of HpD that has been quantitated in biopsies from patients receiving HpD photoradiation therapy. No difference in cellular killing efficiency was observed for power densities of red light varying from 10 to 100 mW/cm2. Cytotoxicity was directly related to O2 tension from 12 to 490 torr with a slight but consistent increase in cell kill at O2 tensions from 7 to 12 torr. Cytotoxicity was effectively quenched by beta-carotene, whereas mannitol had no effect, indicating that cytotoxicity is probably mediated via a mechanism involving singlet oxygen. This information may serve as a basis for more effective application of HpD photoradiation therapy and for designing protocols to study the efficacy of such therapy.
研究了细胞培养中人类胶质瘤细胞的血卟啉衍生物(HpD)光细胞毒性参数,以确定光的最佳波长和功率密度,研究组织氧合的影响,并评估单线态氧和自由基在导致细胞死亡中的作用。细胞存活曲线表明,与红光相比,紫光的相对杀伤效率为12:1。在HpD浓度为10微克/毫升时,需要80焦耳的红光才能产生100%的细胞杀伤,这一HpD水平已在接受HpD光辐射治疗的患者活检中进行了定量。对于10至100毫瓦/平方厘米的红光功率密度,未观察到细胞杀伤效率的差异。细胞毒性与12至490托的氧分压直接相关,在7至12托的氧分压下细胞杀伤略有但持续增加。β-胡萝卜素可有效淬灭细胞毒性,而甘露醇则无作用,表明细胞毒性可能是通过涉及单线态氧的机制介导的。这些信息可作为更有效地应用HpD光辐射治疗以及设计研究此类治疗疗效方案的基础。