The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
Jack Favor - One of the best experts on this subject based on the ideXlab platform.
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the mutagenic activity of Ethylnitrosourea at low doses in spermatogonia of the mouse as assessed by the specific locus test
Mutation Research, 1998Co-Authors: Jack FavorAbstract:Abstract Ethylnitrosourea is the most efficient chemical mutagen in spermatogonial stem cells of the mouse and its mutagenic activity has been intensively studied. The pertinent specific-locus mutation test results for a discussion of low dose–effect studies have been summarized and indicate: (1) A threshold dose response best characterizes the relationship between dose and mutation rate. (2) The reduced effectiveness of Ethylnitrosourea in the low dose range is likely due to a saturable repair process. (3) The recovery of the saturable repair process as assessed in fractionated dose experiments is long (ca. 168 h). The dynamics of stem cell spermatogonia suggests a long time interval before the cell population passes through at least one cell division and this may be relevant to an interpretation of the fractionation effects. (4) There is a slight but important discrepancy between the predicted and observed mutagenic activity of Ethylnitrosourea in the low dose range. This is interpreted to be due to the differences between a mathematical abstraction and the biological realities of the system being studied.
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the effect of the interval between dose applications on the observed specific locus mutation rate in the mouse following fractionated treatments of spermatogonia with Ethylnitrosourea
Mutation Research, 1997Co-Authors: Jack Favor, Angelika Neuhauserklaus, U H Ehling, Andrea Wulff, Albert A Van ZeelandAbstract:Abstract Our earlier analyses have suggested an apparent threshold dose-response for Ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102×C3H)F 1 mice were exposed to 4×10, 2×40, 4×20 or 4×40 mg Ethylnitrosourea per kg body weight with 24 h between applications; 4×40 mg Ethylnitrosourea per kg body weight with 72 h between dose applications; and 2×40, 4×20 and 4×40 mg Ethylnitrosourea per kg body weight with 168 h between dose applications. For all experiments with 24-h intervals between dose applications, there was no effect due to dose fractionation on the observed mutation rates, indicating the time interval between dose applications to be shorter than the recovery time of the repair processes acting on Ethylnitrosourea-induced DNA adducts. In contrast, a fractionation interval of 168 h was associated with a significant reduction in the observed mutation rate due to recovery of the repair process. However, although reduced, the observed mutation rates for fractionation intervals of 168 h were higher than the spontaneous specific-locus mutation rate. These observations contradict the expectation for a true threshold dose response. We interpret this discrepancy to be due to the differences in the predictions of a mathematical abstraction of experimental data and the complexities of the biological system being studied. Biologically plausible explanations of the discrepancy are presented.
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a dose response analysis of Ethylnitrosourea induced recessive specific locus mutations in treated spermatogonia of the mouse
Mutation Research, 1990Co-Authors: Jack Favor, Angelika Neuhauserklaus, M Sund, U H EhlingAbstract:Abstract A dose-response analysis was carried out with 2 independent data sets available for Ethylnitrosourea-induced specific-locus mutations in spermatogonia of the mouse. It was assumed that the occurence of mutation is binomially distributed and maximum-likelihood procedures were employed to determine the appropriateness of 4 alternative models, Linear, Linear-Quadratic, Power, and Threshold, in describing the dependence of the binomial parameter on dose. For both data sets, the Threshold model yielded a far superior fit and the threshold dose was estimated to be between 34 and 39 mg/kg. These results are supported by the relatively inefficient response of Ethylnitrosourea at lower doses in inducing DNA adducts. Relevant specific-locus mutation results in the mouse for low-dose fractionated treatment as well as the recovery of mutation mosaics indicate the threshold model to be an oversimplification. Rather than a threshold dose below which 100% of the induced DNA adducts are repaired, we propose that some DNA adducts which may eventually be fixed as a mutation persist through a number of repair-competent cell divisions and do not interfere with normal cell function nor do they induce a repair response before being eventually fixed as a mutation. We interpret the threshold response for Ethylnitrosourea-induced specific-locus mutations to be due to a saturable repair process which at lower doses results in Ethylnitrosourea being less efficient in inducing mutation. Once this repair process is saturated, a clear dose-related increase in the mutation rate is observed.
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the frequency of dominant cataract and recessive specific locus mutations and mutation mosaics in f1 mice derived from post spermatogonial treatment with Ethylnitrosourea
Mutation Research, 1990Co-Authors: Jack Favor, Angelika Neuhauserklaus, U H EhlingAbstract:Abstract The frequency of dominant cataract and recessive specific-locus mutations and mutation mosaics was determined in F 1 mice derived from post-spermatogonial germ-cell stage treatment with 2 × 80, 160 or 250 mg/kg Ethylnitrosourea. A total of 5 dominant cataract mutations, 3 dominant cataract mutation mosaics, 1 specific-locus mutation and 9 specific-locus mutation mosaics were recovered in 15,542 screened F 1 offspring. Results indicate that Ethylnitrosourea treatment increases the mutation rate of dominant cataract and recessive specific-locus alleles in post-spermatogonial germ-cell stages of the mouse and that the mutations occur mainly as mosaics. Genetic confirmation of newly induced mutations occurring as mosaics is more problemtical for induced recessive alleles than for induced dominant alleles and should be considered when evaluating such mutagenicity results.
U H Ehling - One of the best experts on this subject based on the ideXlab platform.
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the effect of the interval between dose applications on the observed specific locus mutation rate in the mouse following fractionated treatments of spermatogonia with Ethylnitrosourea
Mutation Research, 1997Co-Authors: Jack Favor, Angelika Neuhauserklaus, U H Ehling, Andrea Wulff, Albert A Van ZeelandAbstract:Abstract Our earlier analyses have suggested an apparent threshold dose-response for Ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102×C3H)F 1 mice were exposed to 4×10, 2×40, 4×20 or 4×40 mg Ethylnitrosourea per kg body weight with 24 h between applications; 4×40 mg Ethylnitrosourea per kg body weight with 72 h between dose applications; and 2×40, 4×20 and 4×40 mg Ethylnitrosourea per kg body weight with 168 h between dose applications. For all experiments with 24-h intervals between dose applications, there was no effect due to dose fractionation on the observed mutation rates, indicating the time interval between dose applications to be shorter than the recovery time of the repair processes acting on Ethylnitrosourea-induced DNA adducts. In contrast, a fractionation interval of 168 h was associated with a significant reduction in the observed mutation rate due to recovery of the repair process. However, although reduced, the observed mutation rates for fractionation intervals of 168 h were higher than the spontaneous specific-locus mutation rate. These observations contradict the expectation for a true threshold dose response. We interpret this discrepancy to be due to the differences in the predictions of a mathematical abstraction of experimental data and the complexities of the biological system being studied. Biologically plausible explanations of the discrepancy are presented.
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a dose response analysis of Ethylnitrosourea induced recessive specific locus mutations in treated spermatogonia of the mouse
Mutation Research, 1990Co-Authors: Jack Favor, Angelika Neuhauserklaus, M Sund, U H EhlingAbstract:Abstract A dose-response analysis was carried out with 2 independent data sets available for Ethylnitrosourea-induced specific-locus mutations in spermatogonia of the mouse. It was assumed that the occurence of mutation is binomially distributed and maximum-likelihood procedures were employed to determine the appropriateness of 4 alternative models, Linear, Linear-Quadratic, Power, and Threshold, in describing the dependence of the binomial parameter on dose. For both data sets, the Threshold model yielded a far superior fit and the threshold dose was estimated to be between 34 and 39 mg/kg. These results are supported by the relatively inefficient response of Ethylnitrosourea at lower doses in inducing DNA adducts. Relevant specific-locus mutation results in the mouse for low-dose fractionated treatment as well as the recovery of mutation mosaics indicate the threshold model to be an oversimplification. Rather than a threshold dose below which 100% of the induced DNA adducts are repaired, we propose that some DNA adducts which may eventually be fixed as a mutation persist through a number of repair-competent cell divisions and do not interfere with normal cell function nor do they induce a repair response before being eventually fixed as a mutation. We interpret the threshold response for Ethylnitrosourea-induced specific-locus mutations to be due to a saturable repair process which at lower doses results in Ethylnitrosourea being less efficient in inducing mutation. Once this repair process is saturated, a clear dose-related increase in the mutation rate is observed.
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the frequency of dominant cataract and recessive specific locus mutations and mutation mosaics in f1 mice derived from post spermatogonial treatment with Ethylnitrosourea
Mutation Research, 1990Co-Authors: Jack Favor, Angelika Neuhauserklaus, U H EhlingAbstract:Abstract The frequency of dominant cataract and recessive specific-locus mutations and mutation mosaics was determined in F 1 mice derived from post-spermatogonial germ-cell stage treatment with 2 × 80, 160 or 250 mg/kg Ethylnitrosourea. A total of 5 dominant cataract mutations, 3 dominant cataract mutation mosaics, 1 specific-locus mutation and 9 specific-locus mutation mosaics were recovered in 15,542 screened F 1 offspring. Results indicate that Ethylnitrosourea treatment increases the mutation rate of dominant cataract and recessive specific-locus alleles in post-spermatogonial germ-cell stages of the mouse and that the mutations occur mainly as mosaics. Genetic confirmation of newly induced mutations occurring as mosaics is more problemtical for induced recessive alleles than for induced dominant alleles and should be considered when evaluating such mutagenicity results.
Angelika Neuhauserklaus - One of the best experts on this subject based on the ideXlab platform.
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the effect of the interval between dose applications on the observed specific locus mutation rate in the mouse following fractionated treatments of spermatogonia with Ethylnitrosourea
Mutation Research, 1997Co-Authors: Jack Favor, Angelika Neuhauserklaus, U H Ehling, Andrea Wulff, Albert A Van ZeelandAbstract:Abstract Our earlier analyses have suggested an apparent threshold dose-response for Ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102×C3H)F 1 mice were exposed to 4×10, 2×40, 4×20 or 4×40 mg Ethylnitrosourea per kg body weight with 24 h between applications; 4×40 mg Ethylnitrosourea per kg body weight with 72 h between dose applications; and 2×40, 4×20 and 4×40 mg Ethylnitrosourea per kg body weight with 168 h between dose applications. For all experiments with 24-h intervals between dose applications, there was no effect due to dose fractionation on the observed mutation rates, indicating the time interval between dose applications to be shorter than the recovery time of the repair processes acting on Ethylnitrosourea-induced DNA adducts. In contrast, a fractionation interval of 168 h was associated with a significant reduction in the observed mutation rate due to recovery of the repair process. However, although reduced, the observed mutation rates for fractionation intervals of 168 h were higher than the spontaneous specific-locus mutation rate. These observations contradict the expectation for a true threshold dose response. We interpret this discrepancy to be due to the differences in the predictions of a mathematical abstraction of experimental data and the complexities of the biological system being studied. Biologically plausible explanations of the discrepancy are presented.
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a dose response analysis of Ethylnitrosourea induced recessive specific locus mutations in treated spermatogonia of the mouse
Mutation Research, 1990Co-Authors: Jack Favor, Angelika Neuhauserklaus, M Sund, U H EhlingAbstract:Abstract A dose-response analysis was carried out with 2 independent data sets available for Ethylnitrosourea-induced specific-locus mutations in spermatogonia of the mouse. It was assumed that the occurence of mutation is binomially distributed and maximum-likelihood procedures were employed to determine the appropriateness of 4 alternative models, Linear, Linear-Quadratic, Power, and Threshold, in describing the dependence of the binomial parameter on dose. For both data sets, the Threshold model yielded a far superior fit and the threshold dose was estimated to be between 34 and 39 mg/kg. These results are supported by the relatively inefficient response of Ethylnitrosourea at lower doses in inducing DNA adducts. Relevant specific-locus mutation results in the mouse for low-dose fractionated treatment as well as the recovery of mutation mosaics indicate the threshold model to be an oversimplification. Rather than a threshold dose below which 100% of the induced DNA adducts are repaired, we propose that some DNA adducts which may eventually be fixed as a mutation persist through a number of repair-competent cell divisions and do not interfere with normal cell function nor do they induce a repair response before being eventually fixed as a mutation. We interpret the threshold response for Ethylnitrosourea-induced specific-locus mutations to be due to a saturable repair process which at lower doses results in Ethylnitrosourea being less efficient in inducing mutation. Once this repair process is saturated, a clear dose-related increase in the mutation rate is observed.
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the frequency of dominant cataract and recessive specific locus mutations and mutation mosaics in f1 mice derived from post spermatogonial treatment with Ethylnitrosourea
Mutation Research, 1990Co-Authors: Jack Favor, Angelika Neuhauserklaus, U H EhlingAbstract:Abstract The frequency of dominant cataract and recessive specific-locus mutations and mutation mosaics was determined in F 1 mice derived from post-spermatogonial germ-cell stage treatment with 2 × 80, 160 or 250 mg/kg Ethylnitrosourea. A total of 5 dominant cataract mutations, 3 dominant cataract mutation mosaics, 1 specific-locus mutation and 9 specific-locus mutation mosaics were recovered in 15,542 screened F 1 offspring. Results indicate that Ethylnitrosourea treatment increases the mutation rate of dominant cataract and recessive specific-locus alleles in post-spermatogonial germ-cell stages of the mouse and that the mutations occur mainly as mosaics. Genetic confirmation of newly induced mutations occurring as mosaics is more problemtical for induced recessive alleles than for induced dominant alleles and should be considered when evaluating such mutagenicity results.
Albert A Van Zeeland - One of the best experts on this subject based on the ideXlab platform.
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the effect of the interval between dose applications on the observed specific locus mutation rate in the mouse following fractionated treatments of spermatogonia with Ethylnitrosourea
Mutation Research, 1997Co-Authors: Jack Favor, Angelika Neuhauserklaus, U H Ehling, Andrea Wulff, Albert A Van ZeelandAbstract:Abstract Our earlier analyses have suggested an apparent threshold dose-response for Ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102×C3H)F 1 mice were exposed to 4×10, 2×40, 4×20 or 4×40 mg Ethylnitrosourea per kg body weight with 24 h between applications; 4×40 mg Ethylnitrosourea per kg body weight with 72 h between dose applications; and 2×40, 4×20 and 4×40 mg Ethylnitrosourea per kg body weight with 168 h between dose applications. For all experiments with 24-h intervals between dose applications, there was no effect due to dose fractionation on the observed mutation rates, indicating the time interval between dose applications to be shorter than the recovery time of the repair processes acting on Ethylnitrosourea-induced DNA adducts. In contrast, a fractionation interval of 168 h was associated with a significant reduction in the observed mutation rate due to recovery of the repair process. However, although reduced, the observed mutation rates for fractionation intervals of 168 h were higher than the spontaneous specific-locus mutation rate. These observations contradict the expectation for a true threshold dose response. We interpret this discrepancy to be due to the differences in the predictions of a mathematical abstraction of experimental data and the complexities of the biological system being studied. Biologically plausible explanations of the discrepancy are presented.
Leif G. Salford - One of the best experts on this subject based on the ideXlab platform.
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The RG2 rat glioma model
Journal of Neuro-Oncology, 1995Co-Authors: Arne Brun, Catharina Blennow, Susanne Strömblad, Leif G. SalfordAbstract:The Ethylnitrosourea-induced cell line RG2 grows very well in infinite cell culture in vitro , and provides a simple, reproducible glioma model when inoculated into the brains of syngeneic Fischer 344 rats. We have used this tumor model in a series of therapy studies. We here report our experiences of the untreated (= tumor bearing control) animals, e.g. in terms of the techniques employed and also the growth, histology and effects upon the blood-brain barrier of the tumors. Weight loss as a measure of systemic effects during tumor development is also described. The RG2 model has considerable potential as a suitable tool for experimental neuro-oncology.