Mutagen Testing

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John C. Schimenti - One of the best experts on this subject based on the ideXlab platform.

  • A recombination-based transgenic mouse system for genotoxicity Testing.
    Mutation research, 1994
    Co-Authors: J.ramana Murti, Kerry J. Schimenti, John C. Schimenti
    Abstract:

    Abstract It is well established that Mutagens induce recombination in cultured cells and experimental organisms. Presumably, this is a consequence of the DNA-damage-triggering cellular-repair mechanisms. The relationship between recombination and Mutagenicity has been exploited in submammalian organisms, such as yeast, to assay the ability of chemical agents and radiation to induce a form of recombination called gene conversion - the non-reciprocal transfer of genetic information. This work has demonstrated the efficacy of predicting Mutagenicity on the basis of recombination induction. Here, we describe the utilization of a transgenic mouse system for efficient detection of germ-line gene-conversion events as a Mutagen-screening tool. These mice contain two mutually defective reporter ( lac Z) genes under the regulatory control of a spermatogenesis-specific promoter. A particular intrachromosomal gene conversion event must occur for the generation of functional lac Z activity. Conversion events are visualized by histochemical staining or flow cytometric analysis of transgenic spermatids. The highly Mutagenic compound chlorambucil induced a several fold percentage-wise increase of lac Z--positive spermatids, whereas acrylamide, a weak genotoxin, produced no marked increase in converted spermatids. The results indicate that recombination-based transgenic mouse models for genotoxin screening present a viable option for inexpensive and rapid whole-animal Mutagen Testing. The particular mice were describe may ultimately prove to be a useful tool for identifying agents which can cause heritable genetic mutations in humans.

J.ramana Murti - One of the best experts on this subject based on the ideXlab platform.

  • A recombination-based transgenic mouse system for genotoxicity Testing.
    Mutation research, 1994
    Co-Authors: J.ramana Murti, Kerry J. Schimenti, John C. Schimenti
    Abstract:

    Abstract It is well established that Mutagens induce recombination in cultured cells and experimental organisms. Presumably, this is a consequence of the DNA-damage-triggering cellular-repair mechanisms. The relationship between recombination and Mutagenicity has been exploited in submammalian organisms, such as yeast, to assay the ability of chemical agents and radiation to induce a form of recombination called gene conversion - the non-reciprocal transfer of genetic information. This work has demonstrated the efficacy of predicting Mutagenicity on the basis of recombination induction. Here, we describe the utilization of a transgenic mouse system for efficient detection of germ-line gene-conversion events as a Mutagen-screening tool. These mice contain two mutually defective reporter ( lac Z) genes under the regulatory control of a spermatogenesis-specific promoter. A particular intrachromosomal gene conversion event must occur for the generation of functional lac Z activity. Conversion events are visualized by histochemical staining or flow cytometric analysis of transgenic spermatids. The highly Mutagenic compound chlorambucil induced a several fold percentage-wise increase of lac Z--positive spermatids, whereas acrylamide, a weak genotoxin, produced no marked increase in converted spermatids. The results indicate that recombination-based transgenic mouse models for genotoxin screening present a viable option for inexpensive and rapid whole-animal Mutagen Testing. The particular mice were describe may ultimately prove to be a useful tool for identifying agents which can cause heritable genetic mutations in humans.

Kerry J. Schimenti - One of the best experts on this subject based on the ideXlab platform.

  • A recombination-based transgenic mouse system for genotoxicity Testing.
    Mutation research, 1994
    Co-Authors: J.ramana Murti, Kerry J. Schimenti, John C. Schimenti
    Abstract:

    Abstract It is well established that Mutagens induce recombination in cultured cells and experimental organisms. Presumably, this is a consequence of the DNA-damage-triggering cellular-repair mechanisms. The relationship between recombination and Mutagenicity has been exploited in submammalian organisms, such as yeast, to assay the ability of chemical agents and radiation to induce a form of recombination called gene conversion - the non-reciprocal transfer of genetic information. This work has demonstrated the efficacy of predicting Mutagenicity on the basis of recombination induction. Here, we describe the utilization of a transgenic mouse system for efficient detection of germ-line gene-conversion events as a Mutagen-screening tool. These mice contain two mutually defective reporter ( lac Z) genes under the regulatory control of a spermatogenesis-specific promoter. A particular intrachromosomal gene conversion event must occur for the generation of functional lac Z activity. Conversion events are visualized by histochemical staining or flow cytometric analysis of transgenic spermatids. The highly Mutagenic compound chlorambucil induced a several fold percentage-wise increase of lac Z--positive spermatids, whereas acrylamide, a weak genotoxin, produced no marked increase in converted spermatids. The results indicate that recombination-based transgenic mouse models for genotoxin screening present a viable option for inexpensive and rapid whole-animal Mutagen Testing. The particular mice were describe may ultimately prove to be a useful tool for identifying agents which can cause heritable genetic mutations in humans.

Rosa H. Zhou - One of the best experts on this subject based on the ideXlab platform.

  • Application of urinary Mutagen Testing to detect workplace hazardous exposure and bladder cancer
    Mutation research, 1995
    Co-Authors: Bernard C. K. Choi, J.g. Connolly, Rosa H. Zhou
    Abstract:

    The objectives of this biochemical epidemiologic case-control study were to evaluate urinary Mutagen Testing for occupational exposure assessment, and for possible screening for bladder cancer in the workplace. Thirty-seven patients (19 bladder cancer cases and 18 controls) completed a questionnaire. Two urine samples, i.e. a work sample taken while at work, and a home sample, were requested from each patient. Twenty-six patients (17 cases and 9 controls) gave a total of 47 24-h urine samples for Mutagenicity Testing by the Ames test. A positive Ames test was found to be associated significantly with current occupation with hazardous exposure (odds ratio = 3.7, 95%CI 1.1-12.9), and non-significantly with bladder cancer (odds ratio = 1.8, 95%CI 0.5-7.1). Our results show that the urinary Ames test has the potential of being used as a surveillance for current workplace hazardous exposure (sensitivity = 52%, specificity = 77%, positive predictive value = 72%, negative predictive value = 59%, positive likelihood ratio = 2.3), but not as a screening test for bladder cancer cases (sensitivity = 42%, specificity = 71%, positive predictive value = 3%, negative predictive value = 98%, positive likelihood ratio = 1.5).

T.h. Roderick - One of the best experts on this subject based on the ideXlab platform.

  • Improved Mutagen Testing systems in mice. Final report
    1992
    Co-Authors: T.h. Roderick
    Abstract:

    Our laboratory was the first to induce and ascertain a mammalian chromosomal inversion; we did this by searching for a high frequency of first meiotic anaphase bridges in testes of males whose fathers received post-spermatogonial radiation or Mutagenesis from chromosomal breaking chemical Mutagens. One test in was examined in each mouse, and those showing a high frequency were then mated to determine if the high frequency were passed on as a dominant and whether linkage analysis suggested the presence of an inversion. A very high incidence (exceeding 20% bridges in first meiotic anaphase bridges) was found in about 1 in 150 males examined and this frequency was generally found to be passed on to the offspring an predicted. Later cytological banding techniques were developed elsewhere and we used them to show visually the inverted orders of the inverted chromosomal segments. Since that time we have induced inversions covering most of the mouse genome.

  • Improved Mutagen Testing systems in mice
    1992
    Co-Authors: T.h. Roderick
    Abstract:

    Our laboratory was the first to induce and ascertain a mammalian chromosomal inversion; we did this by searching for a high frequency of first meiotic anaphase bridges in testes of males whose fathers received post-spermatogonial radiation or Mutagenesis from chromosomal breaking chemical Mutagens. One test in was examined in each mouse, and those showing a high frequency were then mated to determine if the high frequency were passed on as a dominant and whether linkage analysis suggested the presence of an inversion. A very high incidence (exceeding 20% bridges in first meiotic anaphase bridges) was found in about 1 in 150 males examined and this frequency was generally found to be passed on to the offspring an predicted. Later cytological banding techniques were developed elsewhere and we used them to show visually the inverted orders of the inverted chromosomal segments. Since that time we have induced inversions covering most of the mouse genome.