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E Gudowska-Nowak

Publications and source records attributed to E Gudowska-Nowak.

10 recordsLinked to original sources
PubMed2006

Lévy-Brownian motion on finite intervals: Mean first passage time analysis.

We present the analysis of the first passage time problem on a finite interval for the generalized Wiener process that is driven by Lévy stable noises. The complexity of the first passage time statistics (mean first passage time, cumulative first passage time distribution) is elucidated together with a discussion of the proper setup of corresponding boundary conditions that correctly yield the statistics of first passages for these non-Gaussian noises. The validity of the method is tested numerically and compared against analytical formulas when the stability index alpha approaches 2, recovering in this limit the standard results for the Fokker-Planck dynamics driven by Gaussian white noise.

Journal Article↗
PubMed2005

Correlation between mitotic delay and aberration burden, and their role for the analysis of chromosomal damage.

The aim was to investigate further the relationship between radiation-induced mitotic delay and the expression of chromosome damage in V79 cells. Recently published data on the time-course of chromosome aberrations in V79 first-cycle metaphases after exposure to 10.4 MeV u(-1) Ar ions (LET = 1226 keV microm(-1)) were supplemented and reanalysed. A statistical analysis of the distribution of aberrations among cells was performed. Furthermore, cells were grouped into subpopulations carrying 0, 1 -2, 3-4, 5- 6 and 7 or more aberrations. Then, based on the mitotic index, the flux of each subgroup through the first mitosis was determined and the average entrance time to mitosis was estimated. For comparison, the flux of aberrant V79 cells generated by X-irradiation was analysed. Analysis of the Ar ion data revealed that the flux of each subpopulation through the first mitosis is strongly affected by its aberration burden, i.e. a positive correlation between the mitotic delay and the number of aberrations carried by a cell was observed. The distribution of aberrations among cells could be well described by Neyman-type A statistics; the corresponding fit parameters also reflect the damage-dependent mitotic delay. Interestingly, comparison of the flux of Ar ion and X-ray-irradiated V79 cells through mitosis revealed (1) that a direct correlation exists between the number of aberrations carried by a cell and its average entrance time to mitosis, and (2) that this effect is independent of the linear energy transfer. The role of these observations for radiation cytogenetics is discussed.

Animals↗
PubMed2004

Cell cycle arrest and aberration yield in normal human fibroblasts. I. Effects of X-rays and 195 MeV u(-1) C ions.

PURPOSE: To examine the relationship between cell proliferation and the expression of chromosomal damage in normal human skin fibroblasts after X-ray and particle irradiation. MATERIALS AND METHODS: Confluent G0/G1 AG1522B cells were exposed to X-rays or 195MeV u(-1) C ions with a linear energy transfer of 16.6 keV microm(-1) in the dose range 1-4 Gy. Directly after irradiation, cells were reseeded at a low density in medium containing 5-bromo-2'-deoxyuridine. At multiple time points post-irradiation, the cumulative BrdU-labelling index, mitotic index and aberration frequency were measured. Based on these data, the total amount of damage induced within the entire cell population was estimated by means of mathematical analysis. RESULTS: Both types of radiation exposure exert a pronounced effect on the cell cycle progression of fibroblasts. They result in delayed entry of cells into S-phase and into the first mitosis, and cause a dramatic reduction in mitotic activity. Measurement of chromosomal damage in first-cycle cells at multiple time points post-irradiation shows that the frequencies of aberrant cells and aberrations increase with time up to twofold for the lower doses. However, for the higher doses, this effect is less pronounced or even disappears. When the data for the whole cell population are analysed, it becomes evident that only a few damaged fibroblasts can progress to the first mitosis, a response attributable at least in part to a long-term arrest of injured cells in the initial G0/G1-phase. As observed in other investigations, the effectiveness of 195 MeV u(-1) C ions was similar or slightly higher than X-rays for all endpoints studied leading to a relative biological effectiveness in the range 1.0-1.4. CONCLUSIONS: Cell cycle arrests affect the aberration yield observable in normal human fibroblasts at mitosis. The data obtained for the cell population as a whole reveal that injured cells are rapidly removed from the mitotically active population through a chronic cell cycle arrest, which is consistent with other studies that indicate that this response is a specific strategy of fibroblasts to minimize the fixation and propagation of genetic alterations.

Apoptosis↗
PubMed2001

Analysis of Ar-ion and X-ray-induced chromatin breakage and repair in V79 plateau-phase cells by the premature chromosome condensation technique.

PURPOSE: The premature chromosome condensation technique has been used to compare chromatin breakage and repair in noncycling V79 cells following high and low LET radiation. MATERIALS AND METHODS: Plateau-phase V79 cells were exposed to graded doses of low energy Ar ions (LET 1233 keV/microm) and X-rays. Cells were fused to mitotic V79 cells immediately after exposure to examine initial chromatin breakage or after various time intervals of post-irradiation incubation to investigate the kinetics of chromatin break rejoining as well as the fraction of unrejoined fragments. RESULTS AND CONCLUSIONS: For both radiation qualities an average initial number of about 2.4 excess PCC fragments per cell per Gy was found increasing linearly with dose. The distributions of PCC chromosomes plus excess fragments among cells followed Poisson statistics after X-ray irradiation, while an overdispersion of the frequencies was observed after Ar-irradiation indicating that a single particle traversal through a cell nucleus can produce multiple chromatin lesions. Moreover, for both radiation types the rejoining of excess fragments has been examined. Both data sets could be fitted well to first-order kinetics with a single component. Despite similar rates of rejoining cellular repair was noticeably less effective for Ar ions than for X-rays. While after 10 h of post-irradiation incubation 60% of Ar ion induced excess fragments remained unrejoined, only 14% of X-ray-induced lesions were not rejoined. Furthermore, comparison of the residual number of excess PCC fragments with recently published data on the yield of chromosome aberrations in first post-irradiation metaphases shows that for both radiation types more aberrations are detected in interphase than in metaphase cells. Yet, for comparable doses this difference is more pronounced for Ar ions indicating that scoring of high LET induced aberrations in metaphase cells might result in a significant underestimation of the produced damage.

Animals↗
PubMed2001

Mathematical models of radiation-induced mitotic delay: time course analysis and statistics of lesions.

Detailed investigations of high and low LET radiation induced chromosome aberrations in various mammalian cell lines have shown that the registered yield of aberrations depends on cell cycle progression delays. The effect of radiation on the cell kinetics can be analyzed in terms of kinetic growth models. The method yields the number of aberrant cells and the number of aberrations as totals obtained after integration over given time-interval.

Animals↗
PubMed2001

High-LET-induced chromosomal damage: time-dependent expression.

Chromosome aberrations are routinely analysed in metaphase cells at one sampling time post-irradiation. Yet, accumulating evidence shows that radiation-induced cycle perturbations and mitotic delay influence the yield of aberrations detectable in mitosis. In extended time-course studies a drastic increase in the number of aberrations with sampling time has been observed after particle irradiation, while after the exposure to sparsely ionizing radiation a less pronounced effect has been found. This difference in the time-course of chromosomal damage is particularly important for the determination of accurate RBE values. As will be discussed, meaningful RBE values for particles can only be obtained, if cells are analysed at multiple sampling times and the complete time-course of aberrations is considered. Otherwise, particle-induced damage will be over- or underestimated. Moreover, depending on the cell system chosen for the analysis, factors like the loss of damaged cells due to apoptosis or a permanent cell cycle arrest complicate the determination of accurate RBE values based on chromosome data.

Animals↗
PubMed2000

High-LET-induced chromosome aberrations in V79 cells analysed in first and second post-irradiation metaphases.

PURPOSE: As an extension of previous studies, the time-course of high-LET-induced chromosomal damage was investigated in first- and second-cycle V79 Chinese hamster cells. MATERIALS AND METHODS: Cells were exposed in G1 to 10.4 MeV/u Ar ions (LET = 1226 keV/microm) and chromosomal damage was measured at 2h sampling intervals between 10 h and 34 h after irradiation. To distinguish between cells in different post-irradiation cycles, the fluorescence-plus-Giemsa technique was applied. RESULTS: For first- and second-generation cells, the number of aberrant metaphases and aberrations per metaphase were found to increase markedly with sampling time, demonstrating that cell cycle progression was delayed according to the number of lesions carried by the cell. To account for the time-dependent expression of chromosomal damage a mathematical approach was used based on the integrated flux of aberrant cells entering mitosis. Moreover, the analysis of Ar ion-induced chromosome lesions confirmed that high-LET radiation results in specific changes in the spectrum of aberration types. In particular, an increased rate of chromatid-type aberrations as well as a high frequency of chromosomal breaks was found, although the cells were exposed in G1. CONCLUSIONS: Due to the fact that cells collected at one sampling time are not representative of the entire population, the complete time-course of chromosomal damage has to be taken into account for the determination of a meaningful RBE value. Otherwise, the analysis of chromosomal damage can result in a pronounced over- or underestimation of the RBE depending on the subpopulation of cells entering mitosis at that particular sampling time.

Animals↗
PubMed1996

Description of interacting channel gating using a stochastic Markovian model.

Single-channel recordings from membrane patches frequently exhibit multiple conductance levels. In some preparations, the steady-state probabilities of observing these levels do not follow a binomial distribution. This behavior has been reported in sodium channels, potassium channels, acetylcholine receptor channels and gap junction channels. A non-binomial distribution suggests interaction of the channels or the presence of channels or the presence of channels with different open probabilities. However, the current trace sometimes exhibits single transitions spanning several levels. Since the probability of simultaneous transitions of independent channels is infinitesimally small, such observations strongly suggest a cooperative gating behavior. We present a Markov model to describe the cooperative gating of channels using only the all-points current amplitude histograms for the probability of observing the various conductance levels. We investigate the steady-state (or equilibrium) properties of a system of N channels and provide a scheme to express all the probabilities in terms of just two parameters. The main feature of our model is that lateral interaction of channels gives rise to cooperative gating. Another useful feature is the introduction of the language of graph theory which can potentially provide a different avenue to study ion channel kinetics. We write down explicit expressions for systems of two, three and four channels and provide a procedure to describe the system of N channels.

Animals↗