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B Fertil

Publications and source records attributed to B Fertil.

At least 37 records · Page 2Linked to original sources
PubMed1995

Correlation between the radiosensitivity in vitro of clones and variants derived from a human melanoma cell line and their spontaneous metastatic potential in vivo.

With an experimental model of spontaneous lung metastases of human melanoma in immunosuppressed newborn rats, a large panel of clones and variants with different metastatic potential were derived from a single human melanoma parental cell line (M4Be). Seven clones and variants from M4Be were selected, respectively, for their low (parental, clone 1), intermediate (clones 2 and 3, subvariant 1-) and high (variant 1, subvariant 1+, clone 4) metastatic potential. This paper investigates the relationship between the in vivo metastatic potential of the eight cell lines and their sensitivity to ionizing radiation in vitro (range 0.05-7 Gy). The radiosensitivity was estimated from the mean inactivation dose, a parameter equal to the area under the survival curve plotted in linear coordinates. Examination of the eight survival curves, obtained with cells cultured for no more than five passages after defrost, shows that clone 1, subvariant 1- and the M4be parental line are the most radioresistant cells, clone 4 and subvariant 1+ are the most radiosensitive cells, while clones 2 and 3 and variant 1 showed an intermediate response to radiation. The metastatic potential in vivo of the parental line and the seven sublines is significantly correlated to their radiosensitivity in vitro: the higher the metastatic potential, the higher the radiosensitivity.

Animals↗
PubMed1995

The beta component of human cell survival curves and its relationship with split-dose recovery.

In principle, alpha and beta can be obtained from single-dose survival curves using standard linear-quadratic fitting; however, alpha and beta being interdependent, it is difficult to evaluate them together with good precision. On the assumption that full recovery from a split-dose treatment gives a result that is the product of the single-dose surviving fraction, it has been suggested that the measurement of split-dose recovery should provide a method to measure beta alone using the formula: beta RR = lnRR/2d2. Most of the studies published to date have been carried out on cancer cell lines or transformed normal cells. We have systematically tested the above proposal on two normal human fibroblast cell lines (HF19 and 1BR3) in two different situations: growing cells, and plateau-phase cells. Two different protocols were used to assess both the potential influence of a priming dose on the surviving cells and the extent of the split-dose recovery. The survival curves generated after different priming doses did not show any significant change in comparison with those achieved without previous irradiation. In addition, the split-dose survival was not different from the square of the corresponding single-dose survival (model free). In these conditions, beta RR's obtained by a linear regression of the recovery ratio data were very similar to the beta's obtained by single doses. However, a curvilinear regression (with a very small negative term at high doses) appears to be more appropriate for cells in plateau phase. This has the result that, as the dose increases, the cell survival curves tend to become less bending than would be expected from the linear-quadratic model; however, the linear-quadratic fitting is still a reasonable characterization of the radiation response since the in vitro colony formation method does not allow measurement of survival < 10(-4).

Cell Division↗
PubMed1995

Surface expression of GD3 disialogangliosides in human melanoma cells is correlated to both metastatic potential in vivo and radiosensitivity in vitro.

With an experimental model of spontaneous lung metastases of melanoma developed in this laboratory, 7 sublines (variants and clones) with different metastatic potential and ganglioside expression were established from a single human melanoma cell line M4Be. Clones and variants derived from M4Be have been characterized at their surface by their gangliosides expression that were determined by flow cytometry with monoclonal antibodies. Gangliosides are membrane glycolipids containing sialic acid. Using an in vitro clonogenic assay and provided that cells were cultured for no more than 5 passages, variations in the cellular radiosensitivity of M4Be and of the 7 sublines were detected. This study shows that the lower the expression of GD3 disialoganglioside at the cell surface, both the higher their radiosensitivity in vitro and their metastatic potential in vivo. These results suggest that highly metastatic human melanoma cells are radiosensitive and deficient in surface gangliosides. Strengthening of this hypothesis arise from experiments showing that the incubation of radiosensitive cells with exogenous ganglioside significantly increases their radioresistance in vitro and reduces their metastatic potential in vivo.

Cell Membrane↗
PubMed1994

Effect of estradiol on endotoxin-induced changes in steroid hormone levels and lethality in male rats.

We examined the effect of exogenous estradiol on the changes in serum steroid hormone levels induced by a nonlethal dose of Escherichia coli endotoxin in male rats and the deaths due to nonlethal and lethal doses of endotoxin. Injection of estradiol 5 min before a nonlethal dose of endotoxin changed the serum sex steroid hormone response of male rats to endotoxin. The serum estrogen concentrations of estradiol + endotoxin-treated rats decreased by 50% (P < 0.001), while those of the endotoxin-treated rats increased (2- to 5-fold). The serum androgen concentrations of estradiol + endotoxin-treated rats did not change significantly, while those of endotoxin-treated rats dropped to 30-40%, P < 0.001. Exogenous estradiol also appeared to influence the percentage of endotoxin-induced deaths in a dose-dependent manner. It reduced the number of deaths induced by nonlethal (2 mg/kg) dose of endotoxin but increased the number of deaths induced by a highly lethal dose (8 mg/kg). These results, together with the known relationships between estrogen and the immune response, suggest that estrogens affect the course of septic shock in a complex fashion and may have either protective or deleterious effect.

Androgens↗
PubMed1994

A benchmark of cell survival models using survival curves for human cells after completion of repair of potentially lethal damage.

Six models of radiation action (the linear-quadratic model, the multitarget model with initial slope, the repair-misrepair model, the lethal-potentially lethal model, the cybernetic model, the saturable repair model) were tested for their goodness of fit to survival curves for human cells. Fifty-three survival curves for human cells irradiated in plateau phase and after completion of repair of potentially lethal damage (PLD) provided the experimental basis for the tests. Three criteria were considered. The capacity to describe the survival data was estimated, using the error left unexplained by the model. A validation of models was achieved by consideration of the mean residual squared errors. The ability of the parameters to characterize survival curves was investigated, studying their variation within and among curves. The models were not equivalent, whatever the test. The saturable repair model and the multitarget with initial slope model gave the most accurate description of survival data. The linear-quadratic model had the most reliable parameters, so that comparisons of the cell survival curves could be made advantageously. The cybernetic model and the lethal-potentially lethal model were found inappropriate for the analysis of survival curves for human cells after completion of PLD repair.

Analysis of Variance↗
PubMed1994

Multiphasic survival curves for cells of human tumor cell lines: induced repair or hypersensitive subpopulation?

Survival of the cells of three human tumor cell lines of differing radiosensitivity was measured after irradiation with single doses of X rays (0.05-5 Gy). At doses below 1 Gy, cells were more radiosensitive than predicted by back-extrapolating the high-dose response. This difference was more marked for cells of the radioresistant cell lines than the radiosensitive cell line so that the "true" initial slopes of the survival curves, at very low doses, were similar for the cells of the three cell lines. This phenomenon could reflect an induced radioresistance so that low doses of X rays are more effective per gray than higher doses, because only at higher doses is there sufficient damage to trigger repair systems or other radioprotective mechanisms which can then act during the time course for repair of DNA injury.

Cell Survival↗
PubMed1993

Predictive value of in vitro radiosensitivity parameters in head and neck cancers and cervical carcinomas: preliminary correlations with local control and overall survival.

PURPOSE: To determine whether in vitro radiosensitivity parameters are predictive of treatment outcome. METHODS AND MATERIALS: Biopsies were obtained from patients with head and neck cancers (57) and cervical carcinomas (20) and in vitro radiosensitivity parameters were obtained using the CAM plate assay. RESULTS: In most cases (75%) patients were treated with radiation alone. The median follow up was 461 days. When the whole group of head and neck cancers and cervical carcinomas was considered, patients with a SF2 value below 0.36 had a higher 2-year local control rate (93% versus 68%) and a higher 2-year survival rate (71% vs. 62%) than those with SF2 values above that threshold, but differences were not significant. These trends persisted when head and neck cancers were considered alone with a higher local control rate (86% vs. 67%) and a higher survival rate (75% vs. 52.5%) obtained for patients with a SF2 value below 0.36. When the alpha value was evaluated for the whole group of patients a significantly higher local control rate (80.5% vs. 40.5%) and overall survival rate (71% versus 37.5%) at 2 years were obtained for patients with alpha values above 0.07 Gy-1. When only the group of head and neck cancers was considered, local control rate was significantly higher (79% vs. 33%) but overall survival rate (65.5% vs. 33%) was not significantly higher for alpha values above 0.07 Gy-1. CONCLUSION: These results are encouraging but need to be confirmed with a larger number of patients with a longer follow-up.

Carcinoma, Squamous Cell↗
PubMed1993

Hypersensitivity of a human tumour cell line to very low radiation doses.

Survival of HT29 cells was measured after irradiation with single doses of X-rays (0.05-5 Gy) and neutrons (0.025-1.5 Gy), using a Dynamic Microscopic Imaging Processing Scanner (DMIPS) with which individual cells can be accurately located in tissue culture flasks, their positions recorded, and after an appropriate incubation time the recorded positions revisited to allow the scoring of survivors. The response over the X-ray dose range 2-5 Gy showed a good fit to a Linear-Quadratic (LQ) model. For X-ray doses below 1 Gy, an increased X-ray effectiveness was observed with cell survival below the high-dose LQ prediction. The value of --dose/loge (SF) for each experimental data point, plotted against dose, demonstrated clearly how X-rays are maximally effective at doses approaching zero, becoming less effective as the dose increases and with minimal effectiveness at about 0.6 Gy then becoming more effective again as the dose increases above 1.5 Gy. This phenomenon was not seen with neutrons. Neutron RBE was calculated for each X-ray data point by taking each X-ray survival value and comparing it with the common LQ fit to all the neutron data. Over the X-ray dose range 0.05-0.2 Gy, the RBE is close to 1 indicating that these very low doses of X-rays are of similar effectiveness to neutrons in killing cells. The increase in RBE with increasing dose over the range 0.05-1 Gy, and the slight decrease in RBE above 1 Gy, reflect primarily the changes in X-ray sensitivity over the whole dose range of 0.05-5 Gy. Several arguments suggest that this phenomenon could reflect an induced radioresistance so that in this system low single doses of X-rays are more effective per Gy than higher doses in reducing cell survival because only at higher doses, above a threshold, is there sufficient damage to trigger radioprotective mechanisms.

Cell Survival↗
PubMed1991

Exploratory analysis of population pharmacokinetic data from clinical trials with application to isradipine.

Drug level monitoring during routine clinical visits in the course of phase III trials provides a means to document pharmacokinetic variability in a patient population. Such a pharmacokinetic screen was performed for the new calcium antagonist isradipine. A total of 697 blood samples were collected at any time after the morning dose from 252 patients who had received oral doses of isradipine. Three approaches of data analysis based on exploratory (graphical and statistical) techniques were used to relate plasma level to patient demographic data and laboratory parameters. The pharamacokinetics of isradipine seemed to be influenced by the demographic variables of age (already detected in conventional studies) and weight, as well as by the blood serum levels of inorganic phosphorous, uric acid, alkaline phosphatase, and bilirubin, but only to a small, clinically irrelevant extent. The findings from the three approaches were complementary. They suggest that a pharmacokinetic screening in clinical trials is feasible at reasonable experimental cost and effort and provides useful data on interindividual and intraindividual pharmacokinetic variability in patients.

Adult↗
PubMed1990

The relationship between radiosensitivity and repair of potentially lethal damage in human tumor cell lines with implications for radioresponsiveness.

The relationship between intrinsic radiosensitivity and repair capacity was studied for 22 human tumor cell lines in vitro. The experimental material was taken from 19 published papers. Parameters from three radiobiological models were used to assess this relationship: the one-hit multitarget model (D0 and n), the linear-quadratic model (alpha and beta), and the mean inactivation dose (D). Data were obtained for cells in three stages: exponentially growing cells (exp), plateau-phase cells plated immediately after irradiation (ip), and plateau-phase cells plated after completion of PLD repair (dp). No significant difference was found between radiosensitivity of exp and ip cells. There was no correlation between repair capacity and intrinsic radiosensitivity assessed with plateau-phase cells plated immediately after irradiation. The correlation studies between intrinsic radiosensitivity or repair capacity and clinical responsiveness were achieved by assigning cell lines to one of three groups of decreasing in vivo radioresponsiveness: highly, medium, and poorly responsive. There was a significant correlation between radiosensitivity and radioresponsiveness, but no correlation between repair capacity and radioresponsiveness. The average repair capacity was about 0.6 Gy, in terms of D. Three parameters, the mean inactivation dose of exponentially growing cells, of plateau-phase cells plated immediately after irradiation, and of plateau-phase cells plated after completion of PLD repair, could be used equally to assess the relationship between in vitro data and radioresponsiveness. The present results are compared to those obtained in a similar study on a group of 48 nontransformed fibroblast cell strains.

Analysis of Variance↗
PubMed1989

The relationship between potentially lethal damage repair and intrinsic radiosensitivity of human cells.

The intrinsic radiosensitivity of exponentially growing cells (exp) was compared to that of immediately plated plateau phase cells (ip) using published data on 60 human cell lines (27 fibroblast lines and 33 tumour cell lines). The values for alpha, D and S2 are not significantly different for the two groups; beta is significantly higher in ip cells. This produces a smaller alpha/beta ratio in ip cells than in exp cells. The influence of potentially lethal damage (PLD) repair was assessed by comparing the radiosensitivities of ip cells and plateau phase cells with delayed plating (dp). The published data for 81 human cell lines (48 fibroblasts and 33 tumour lines) were used. PLD repair was found to lead to a decrease in alpha and an increase in D and S2, whereas neither beta nor the alpha/beta ratio changed significantly. The relationship between PLD repair and intrinsic radiosensitivity was assessed by repair capacity and the repair ratio. The fitted relationship is a bell-shaped curve with a maximum at 2.2 Gy for repair capacity. The fitted curve predicts that repair capacity is zero at a D up of 0.28 Gy and at 4 Gy. Thus, PLD repair is a reasonable reflection of intrinsic radiosensitivity up to 2.2 Gy. Above 2.2 Gy, the relationship is reversed: the greater the radioresistance, the lower the PLD repair.

Cell Cycle↗
PubMed1988

Correlation between PLD repair capacity and the survival curve of human fibroblasts in exponential growth phase: analysis in terms of several parameters.

Published data on the in vitro radiosensitivity of 46 nontransformed fibroblasts of different genetic origins studied in plateau phase with immediate or delayed plating were used to investigate to what extent potentially lethal damage repair capacity is related to intrinsic radiosensitivity (i.e., irradiated in exponential growth phase). While most of the survival curve analysis is conducted in terms of D0, Dq, and the mean inactivation dose D, some of the data are also discussed in terms of the linear-quadratic model parameter alpha. Using D it is shown that: (i) the radiosensitivity of human fibroblasts in exponential growth phase does not significantly differ from that of plateau-phase fibroblasts with immediate plating; (ii) the radiosensitivity of plateau-phase cells with delayed plating is correlated to the radiosensitivity of cells with immediate plating: the more radioresistant the cell strain in exponential growth phase, the higher its repair capacity; (iii) the repair capacity of the cell strains is related to their genetic origin. In conclusion, we suggest that the survival curve of growing cells depends on the repair capacity of the cells.

Ataxia Telangiectasia↗
PubMed1987

Initial slope of radiation survival curves is characteristic of the origin of primary and established cultures of human tumor cells and fibroblasts.

The published survival curves of 110 human tumor cell lines and 147 nontransformed human fibroblast strains have been reanalyzed using three different statistical methods: the single hit multitarget model, the linear-quadratic model, and the mean inactivation dose. The 110 tumor cell lines were classified in two ways: (a) into three categories defined by clinical radiocurability criteria, and (b) into seven categories based on histopathology. The 147 fibroblast strains were divided into eight genetic groups. Differences in the radiosensitivities of both the tumor cell and fibroblast groups could be demonstrated only by parameters that describe the slopes of the initial part of the survival curves. The capacity of the survival level to identify significant differences between groups was dose dependent over the range 1 to 6 Gy. This relationship showed a bell-shaped curve with a maximum at 1.5 Gy for the tumor cell lines and 3 Gy for the fibroblasts. Values for intrinsic radiosensitivity for a number of groups of tumors have also been obtained by primary culture of tumor cells. These values are strictly comparable to those obtained by clonogenic methods. This confirms that intrinsic radiosensitivity is a determinant of the response of tumor cells to radiotherapy and suggests that tissue culture methods may be used as a predictive assay.

Cell Line↗
PubMed1986

Distribution of radiation sensitivities for human tumor cells of specific histological types: comparison of in vitro to in vivo data.

The radiosensitivities of human tumor cell lines, grouped into 6 histological categories, have been studied using data from the published literature. The parameters alpha, beta, n, D0, D, and the surviving fraction to 2 Gy (S2) and 8 Gy (S8) were calculated. Only the two parameters mainly derived from the initial part of the survival curve, alpha and D, together with S2, provided data which were correlated with the clinical radioresponsiveness of each histological group. Thus, there are intracellular factors which influence clinical radioresponsiveness whose relative importance varies from one histological cell type to another. The value of D gave the most precise characterization of the average group radiosensitivity. It was possible to compare the in vivo radiosensitivities of non-severely hypoxic cells with those of tumor cells irradiated in vitro for 7 tumor lines grown as xenografts in mice. The average radiosensitivity was 1.9 times less in vivo than in vitro. This difference indicates that, in addition to the intrinsic factors of radioresistance demonstrated in vitro, and independently of severe hypoxia, there are other factors which specifically reduce radiosensitivity in vivo.

Adenocarcinoma↗
PubMed1986

Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins.

A statistical analysis of the radiosensitivity of 204 different survival curves of nontransformed human fibroblast cell strains of different genetic origins was made using three criteria: the multi-target one-hit model (characterized by parameters n and D0), the surviving fraction for a 2 Gy dose (S2) and the mean inactivation dose (D). D is found to be the best parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and for discrimination between groups of cell strains of differing radiosensitivity. Its use allows the description of a range of 'normal' radiosensitivity for control fibroblasts and the classification of the various genetic disorders as a function of their mean radiosensitivity expressed in terms of D. Nine groups of cell strains appear to exhibit radiosensitivity which differs significantly from that of the controls: seven groups are hypersensitive (ataxia-telangiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and from individuals with chromosome 13 anomalies). Since the coupled parameter n and D0 failed to discriminate between the radiosensitivity of the different genetic groups, we recommend the use of D to make an intercomparison of intrinsic radiosensitivity of nontransformed human fibroblasts.

Cell Line↗
PubMed1985

Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves.

One hundred and one published survival curves for 92 human cell lines (including 64 tumor lines) have been analyzed in terms of several parameters that are supposed to characterize cell radiosensitivity. Values for n, Do, alpha and beta (from the linear quadratic model), D (Mean Inactivation Dose), and survivals at 2 Gy and 8 Gy have been obtained for each curve. It was found that: I. the initial part of the survival curve is specific to the corresponding cell line; II. this initial part is well characterized by the parameters alpha and D, the values of which can be used to compare intrinsic radiosensitivity among human cell lines; III. human tumor cell line radiosensitivity (expressed in terms of alpha, D and survival at 2 Gy) reflects the clinical radioresponsiveness of the tumors from which the cell lines are derived. Thus, cells from tumors with low radioresponsiveness (melanomas and glioblastomas) are the less radiosensitive. Furthermore, the range of survival at a dose of 2 Gy is broad enough to account, in large measure, for observed differences in clinical tumor radioresponsiveness.

Cell Line↗
PubMed1984

Abnormal sensitivity of some Cockayne's syndrome cell strains to UV- and gamma-rays. Association with a reduced ability to repair potentially lethal damage.

Cockayne's syndrome (CS) is a rare autosomal recessive genetic disease characterized by mental and physical retardation, microcephaly, dwarfism, retinitis pigmentosa and a hypersensitivity to sunlight. Cells originating from patients also exhibit, in vitro, a hypersensitivity to UV radiation. Using a colony assay in vitro, we studied the sensitivity of 5 CS cell strains (GM739, BOR, CS697, CS698 and KA) and two normal ones (HF19 and GP) to UV- and gamma-irradiation. The 5 CS strains appear to be UV-hypersensitive but the sensitivity varies widely from one strain to another. Hypersensitivity to gamma-rays has been reported for 4 out of the 5 CS cell strains investigated. However, these CS cell strains are less sensitive to gamma-rays than are ataxia telangiectasia cells. The KA cell strain exhibits a normal response to gamma-irradiation. Repair of potentially lethal damage (PLD) after UV- and gamma-irradiation was investigated by using unfed plateau-cell cultures. Under these conditions, control cells show a great capacity to repair PLD (10- to 30-fold survival increase at 1% survival level). The two CS strains (GM739 and BOR), which are hypersensitive to both UV- and gamma-irradiation, exhibit no or only little PLD repair after treatment. In contrast, the normal response of KA cells to gamma-rays is associated with a normal PLD repair capability. This latter cell strain exhibits an intermediate sensitivity to UV and shows an intermediate PLD repair capacity. The response of CS cell strains after gamma-irradiation suggests a genetic heterogeneity. Three complementation groups are described in CS cells when dealing with UV radiosensitivity. However, variations in gamma-ray sensitivity are reported for cells within the same UV complementation group.

Cell Survival↗