DNA LESIONS AND DNA DEGRADATION IN MOUSE LYMPHOMA L5178Y CELLS AFTER PHOTODYNAMIC TREATMENT SENSITIZED BY CHLOROALUMINUM PHTHALOCYANINE

Two closely related strains of mouse lymphoma L5178Y cells, LY-R and LY-S, have been found to differ in their sensitivity to the cytotoxic effects of photodynamic treatment (PDT) with chloroaluminum phthalocyanine (CAPC) and red light. Strain LY-R is more sensitive to photodynamic cell killing than strain LY-S. Differences in uptake of CAPC could not account for the differences in cytotoxic effects. There was no marked difference between the two strains in the induction of single-strand breaks (which includes frank single-strand breaks and alkali-labile lesions), but substantially more DNA-protein cross-links were formed in strain LY-R by CAPC and light. Repair of single-strand breaks proceeded with similar kinetics in both strains for the first 30 min post-irradiation, suggesting that these lesions are not responsible for the differential sensitivity of the two strains to the lethal effects of photodynamic treatment. Thereafter, alkaline elution revealed the presence of increasing DNA strand breakage in strain LY-R. DNA degradation, as measured by the conversion of prelabeled [14C] DNA to acid-soluble radioactivity, was more rapid and extensive in strain LY-R.     

基于符号动力学的耦合映像格子系统的初值估计

在符号动力学的基础上,深入探讨了基于动力学符号序列的局部耦合映像格子系统求逆问题.在理论上系统地分析耦合映像系统初值估计的性能与耦合系数及映射函数之间的数学关系,证明相空间I^M上的任意取值通过基于符号向量序列的逆迭代过程并不一定收敛至初值,其敛散性与耦合强度和映射函数的选择有直接关系.同时证明了混沌或其拓扑共轭的逆不一定为压缩映射,其总体的敛散性与整个逆迭代过程中的收敛与发散的强度对比有关.理论分析与数值实验结果完全一致,说明本文提出的耦合映像格子系统初值估计问题的分析 关键词： 耦合映像格子 符号动力学 初值估计     

基于时变耦合映像格子模型的信号初值估计

从耦合映像格子中,恢复系统初始条件是耦合系统求逆问题,也是信号处理研究中的一个关键性问题.本文在符号动力学方法的基础上,对映像系数进行修正,针对耦合单峰Logistic映射,提出一种基于时变映像系数恢复信号初值的新方法.在映像过程无噪或受到高斯白噪声污染时,本文方法都能够较好地恢复信号初值的统计特性,而且具有较小的偏差和均方误差,并与原信号之间具有较强的相关性,从而能够更好和更加合理地刻画实际信号的物理过程,对系统初值做出更优的估计. 关键词： 耦合映像格子 恢复初值的统计特性 时变映像系数     

Variation in Photodynamic Efficacy during the Cellular Uptake of Two Phthalocyanine Photosensitizers

A decrease in the efficacy of photodynamic therapy (PDT) with phthalocyanine photosensitizers was observed for lymphoblastic murine and human cell lines as the time between the addition of the photosensitizer, aluminum phthalocyanine (AlPc), to the culture medium and exposure to light was increased from 4 h to 18 h. The total intracellular concentration of photosensitizer did not decrease significantly during this 18 h interval. For the murine cell lines, the maximum cytotoxic and mutagenic effects were observed when the time between addition of the photosensitizer and irradiation was between 1 and 4 h. The time course of the variations in efficacy did not vary greatly from one murine cell line to another, even though the cell lines differ markedly in the extent of their cytotoxic and mutagenic response. The time course of the variation was similar for cytotoxicity and mutagenicity, as well as for the induction of DNA fragmentation. The human lymphoblastic cell line, WTK1, showed less variation in survival and mutability with time than did the murine cell lines. With Pc 4 (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) as the photosensitizer, the photocytotoxicity for murine L5178Y (LY)-Sl cells did not change significantly as the time between addition of Pc 4 and irradiation was increased from 2 to 18 h. However, the mutagenicity decreased by a factor of three during this interval. The mutagenicity of PDT with Pc 4 was much less in LY-Sl cells than that with AlPc. The results suggest that the variation in the efficacy observed for AIPc-induced photocytotoxicity is caused by changes in the intracellular distribution and/or the aggregation of the photosensitizer with time after its addition.     

Mutagenicity of Photodynamic Therapy as Compared to UVC and Ionizing Radiation in Human and Murine Lymphoblast Cell Lines

Abstract— The mutagenicity of photodynamic therapy (PDT) using red light and either Photofrin® (porfimer sodium) (PF) or aluminum phthalocyanine (AIPc) as the photosensitizer was determined at the thymidine kinase (TK) locus in the human lymphoblastic cell lines, TK6 and WTK1, and was compared to the mutagenicity of UVC and X-radia-tion in these cells as well as the mutagenicity of PDT in murine L5178Y lymphoblastic cell lines. Photodynamic therapy was found not to be mutagenic in TK6 cells, which possess an active p53 gene and which are relatively deficient in recombination and repair of DNA double-strand breaks. In contrast, PDT with either sensitizer was significantly mutagenic in WTK1 cells, which harbor an inactivating mutation in the p53 gene and are relatively efficient in recombination and double-strand break repair as compared to TK6 cells. The induced mutant frequency in WTK1 cells with PF as the photosensitizer was similar to that induced by UVC radiation but lower than that induced by X-radiation at equitoxic faiences/ doses. The mutant frequency induced by PDT in WTK1 cells with either photosensitizer was much lower than that induced in murine lymphoblasts at equitoxic fluences. The TK6 and WTK1 cells did not differ in their sensitivity to the cytotoxic effects of PDT, but the level of PDT-induced apoptosis was greater in TK6 than in WTK1 cells. These results indicate that the mutagenicity of PDT varies in different types of cells and may be related to the repair capabilities as well as the p53 status of the cells.     

A method of estimating initial conditions of coupled maplattices based on time-varying symbolic dynamics

A novel computationally efficient algorithm in terms of the time-varying symbolic dynamic method is proposed to estimate the unknown initial conditions of coupled map lattices (CMLs). The presented method combines symbolic dynamics with time-varying control parameters to develop a time-varying scheme for estimating the initial condition of multi-dimensional spatiotemporal chaotic signals. The performances of the presented time-varying estimator in both noiseless and noisy environments are analysed and compared with the common time-invariant estimator. Simulations are carried out and the obtained results show that the proposed method provides an efficient estimation of the initial condition of each lattice in the coupled system. The algorithm cannot yield an asymptotically unbiased estimation due to the effect of the coupling term, but the estimation with the time-varying algorithm is closer to the Cramer--Rao lower bound (CRLB) than that with the time-invariant estimation method, especially at high signal-to-noise ratios (SNRs).