Heritable translocation test in mice

Generoso, W.M.; Bishop, Jack B.; Gosslee, D.G.; Newell, Gordon W.; Sheu, C.W.; Halle, E. Von

doi:10.1016/0165-1110(80)90010-x

Cited by 85 publications

(21 citation statements)

References 49 publications

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“…Extrapolation from animal data has been used in an effort to understand IRinduced germline mutations in humans due to the inherent difficulties in human epidemiological studies involving germ cells [1]. Several rodent assays are capable of detecting germline mutation, including the specific locus (SL) test [2], heritable translocation (HT) assay [3], dominant lethal (DL) assay [4], expanded simple tandem repeats (ESTRs) assay [5], and transgenic rodent assays [6,7]. The traditional mutation assays, e.g.…”

Section: Introductionmentioning

confidence: 99%

Recovery of a low mutant frequency after ionizing radiation-induced mutagenesis during spermatogenesis

Intano

McCarrey

et al. 2008

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Humans are exposed to ionizing radiation (IR) under various circumstances, e.g. cosmic radiation, diagnostic X-rays and radiotherapy for cancer. It has been shown that IR can impair spermatogenesis and can cause mutations in germ cells. However, the mutagenic responses of germ cells exposed to IR at different stages of testicular maturation have not been examined by directly assessing the mutant frequency in defined spermatogenic cell types. This study was performed to address whether preadult exposure to IR can increase mutations in adult germ cells that could in turn have a major impact on adult reproductive function and the health of ensuing offspring. Male Lac I transgenic mice were irradiated with a single dose of 2.5 Gy of γ-ray at different ages before adulthood, reflecting different stages of testicular maturation, and then mutant frequency (MF) was determined directly in spermatogenic cell types emanating from the irradiated precursor cells. The results showed that (1) preadult exposure to IR did not significantly increase MF in adult epididymal spermatozoa; (2) spermatogenic stages immediately following the irradiated stage(s) displayed an elevated mutant frequency, but (3) the mutant frequency was restored to unirradiated levels in later stages of spermatogenesis. These findings provide evidence that there is a mechanism(s) to prevent spermatogenic cells with elevated mutant frequencies from progressing through spermatogenesis.

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Section: Introductionmentioning

confidence: 99%

Recovery of a low mutant frequency after ionizing radiation-induced mutagenesis during spermatogenesis

Intano

McCarrey

et al. 2008

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…At about 13 days in the mouse, however, the female germ cells begin to enter meiotic prophase (19,60), and by birth, all oocytes are in late pachytene, diplotene, and the arrested state of diffuse diplotene (dictyate). All oocytes enter the diffuse diplotene stage within a few days after birth.…”

Section: Female Normal Oogenesismentioning

confidence: 99%

“…From there, they migrate to the germinal ridges by route of the dorsal mesentery (12,19,60,99). Mitotic division occurs both during migration of the germ cells, and after they reach the germinal ridges.…”

Section: Normal Gametogenesis: Malementioning

confidence: 99%

Dominant-Lethal Mutations and Heritable Translocations in Mice

Generoso

1984

Mutation, Cancer, and Malformation

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By acceptance of t h i s a r t i c l e , t h e publisher o r r e c i p i e n t acknowledges t h e U.S. Government's r i g h t t o r e t a i n a nonexclusive, r o y a l t y -f r e e l i c e n s e i n and t o any copyright covering tke a r t i c l e . U.S. Department of Energy under c o n t r a c t W-7405-eng-26 w i t h t h e UnionCarbide Corporation. SUMMARYThe primordial germ cells originate in the regloti of the caudal end of the primitive streak, root of the allantois, and yolk sac splanchuopleure, and migrate to the gonadal ridges where they divide to form the oogonia of the female and gonocytes of the male. In the female, the transition to oocytes occurs in utero, and the female mammal is born with a finite number of oocytes that cannot be replaced. By contrast, the gonocytes of the male initiate divisions soon after birth to form the spermatogonial stem cells, which persist throughout reproductive life of the male and are capable of regenerating the seminiferous epithelium after injury. As a result of these basic differences in gametogenesis, the response of the male and female to radiation and chemicals is different. Any loss of oocytes in the female cannot be replaced, and if severe enough, will result in a shortening of the reproductive span. In the male, a temporary sterile period may be induced owing to destruction of the differentiating spermatogonia, but the stem cells are the most resistant spermatogonial type, are capable of repopulating the seminiferous epithelium, and fertility usually returns. The response of both the male and female changes with development of the embryonic to the adult gonad, and with differentiation and maturation in the adult. The primordial germ cells, early oocytes, and differentiating spermatogonia of the adult male are unusually sensitive to the cytotoxic action of noxious agents, but each agent elicits a specific response owing to the intricate biochemical and physiological changes associated with development and maturation of the gametes. The relationship of germ cell killing to fertility is direct, and long-term fertility effects can be predicted from histological analysis of the gonads. The relationship to genetic effects on the other hand, is indirect, and acts primarily by limiting the cell stages available for testing, by affecting the distribution of mitotically active stem cells among the different stages of the mitotic cycle, and thereby, changing both the type and frequency of genetic effects observed. INTRODUCTIONThe level of our understanding of the effect of radiation, chemicals, pollutants, and noxious agents in general on the gonads, and the relationship of these effects to fertility and to transmission of genetic damage is dependent upon our understanding of the normal process of germ cell development. Some of the problems to be discussed here were phrased over a century ago, but it is only within the last thirty years that the direct lineage between primordial germ cells and the definitive gametes has been firmly established, and significant progress i...

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“…More than a dozen chemicals have been shown to induce transmissible translocations in the mouse (3,30 (35,36). Of the chemicals evaluated to date, all appear to have their predominant or strongest effect on post-stemcell stages (i.e., spermatocytes, spermatids, spermatozoa) in producing transmitted germ-line translocations (30,32,34 (36).…”

Section: Chromosomal Rearrangementsmentioning

confidence: 99%

“…Of the chemicals evaluated to date, all appear to have their predominant or strongest effect on post-stemcell stages (i.e., spermatocytes, spermatids, spermatozoa) in producing transmitted germ-line translocations (30,32,34 (36).…”

Section: Chromosomal Rearrangementsmentioning

confidence: 99%

Genetic Anomalies in Mammalian Germ Cells and Their Significance for Human Reproductive and Developmental Risk

Dellarco¹

1993

Environmental Health Perspectives

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Heritable translocation test in mice

Cited by 85 publications

References 49 publications

Recovery of a low mutant frequency after ionizing radiation-induced mutagenesis during spermatogenesis

Recovery of a low mutant frequency after ionizing radiation-induced mutagenesis during spermatogenesis

Dominant-Lethal Mutations and Heritable Translocations in Mice

Genetic Anomalies in Mammalian Germ Cells and Their Significance for Human Reproductive and Developmental Risk

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