Mutations induced in male germ cells after treatment of transgenic mice with ethylnitrosourea

Katoh, Masaya; Horiya, N.; Valdivia, R.

doi:10.1016/s1383-5718(96)00121-0

Cited by 18 publications

(11 citation statements)

References 18 publications

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“…Male germ cells go through an intricate differentiation process in an orderly progression, and the entire process takes about 42 days in mice to proceed from spermatogonial stem cells to mature sperm (Adler, 1996;Ashby et al, 1997;Ghanayem et al, 2005;Shelby and Tindall, 1997;Singer et al, 2006). Using Big Blue mice, it has been demonstrated that the spermatogonial stem cells are more sensitive to ethylnitrosourea (ENU)-induced mutagenesis than the spermatocytes, spermatids, and spermatozoa, based on ENU-induced MFs using pooled vas deferens sperm or the caudal epididymal sperm from six to nine mice collected at 3, 14, 22, or 93 days after treatment (Katoh et al, 1997). In addition, the MF detected in whole testes was similar to that detected in the vas deferens sperm or caudal epididymal sperm (Katoh et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Using Big Blue mice, it has been demonstrated that the spermatogonial stem cells are more sensitive to ethylnitrosourea (ENU)-induced mutagenesis than the spermatocytes, spermatids, and spermatozoa, based on ENU-induced MFs using pooled vas deferens sperm or the caudal epididymal sperm from six to nine mice collected at 3, 14, 22, or 93 days after treatment (Katoh et al, 1997). In addition, the MF detected in whole testes was similar to that detected in the vas deferens sperm or caudal epididymal sperm (Katoh et al, 1997). In this study, we collected testes 3 weeks after 4 weeks of treatment (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Mutagenicity of Acrylamide and Glycidamide in the Testes of Big Blue Mice

Wang

McDaniel

Manjanatha

et al. 2010

Toxicological Sciences

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Acrylamide (AA) is an industrial chemical, a by-product of fried starchy foods, and a mutagen and rodent carcinogen. It can also cause damage during spermatogenesis. In this study, we investigated whether AA and its metabolite glycidamide (GA) induce mutagenic effects in the germ cells of male mice. Male Big Blue transgenic mice were administered 1.4 or 7.0mM of AA or GA in the drinking water for up to 4 weeks. Testicular cII mutant frequency (MF) was determined 3 weeks after the last treatment, and the types of the mutations in the cII gene were analyzed by DNA sequencing. The testes cII MFs in mice treated with either the low or high exposure concentrations of AA and GA were increased significantly. There was no significant difference in the cII MFs between AA and GA at the low exposure concentration. The mutation spectra in mice treated with AA (1.4mM) or GA (both 1.4 and 7.0mM) differed significantly from those of controls, but there were no significant differences in mutation patterns between AA and GA treatments. Comparison of the mutation spectra between testes and livers showed that the spectra differed significantly between the two tissues following treatment with AA or GA, whereas the mutation spectra in the two tissues from control mice were similar. These results suggest that AA possesses mutagenic effects on testes by virtue of its metabolism to GA, possibly targeting spermatogonial stem cells, but possibly via different pathways when compared mutations in liver.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mutagenicity of Acrylamide and Glycidamide in the Testes of Big Blue Mice

Wang

McDaniel

Manjanatha

et al. 2010

Toxicological Sciences

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“…Phage carrying mutations in the Lac I gene are identified as blue plaques on E. coli lawns plated on agarose containing the chromogenic substrate 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside (X-gal). The LacI transgenic rodent model is being applied in increasing numbers of in vivo mutagenesis studies [7,[10][11][12][13][14][15]. However, there is a paucity of information regarding IR-induced germline mutagenesis in Lac I transgenic mice.…”

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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“…Future mouse models will no doubt provide more precise control over gene expression at various stages of development. As we understand more about the expression profiles of genes through embryogenesis, it is also becoming possible to activate mutant alleles at precise points in the developmental programme, for example through the use of inducible Cre‐Lox technology 124, 125. Inevitably, some problems remain with these technologies.…”

Section: Discussionmentioning

confidence: 99%

New approaches for modelling cancer mechanisms in the mouse

Maddison

Clarke

2005

The Journal of Pathology

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Mouse models of human cancer are vital to our understanding of the neoplastic process, and to advances in both basic and clinical research. Indeed, models of many of the major human tumours are now available and are subject to constant revision to more faithfully recapitulate human disease. Despite these advances, it is important to recognize that limitations do exist to the current range of models. The principal approach to modelling has relied upon the use of constitutive gene knockouts, which can often result in embryonic lethality, can potentially be affected by developmental compensation, and which do not mimic the sporadic development of a tumour expanding from a single cell in an otherwise normal environment. Furthermore, simple knockouts are usually designed to lead to loss of protein function, whereas a subset of cancer-causing mutations clearly results in gain of function. These drawbacks are well recognized and this review describes some of the approaches used to address these issues. Key amongst these is the development of conditional alleles that precisely mimic the mutations found in vivo, and which can be spatially and tissue-specifically controlled using 'smart' systems such as the tetracycline system and Cre-Lox technology. Examples of genes being manipulated in this way include Ki-Ras, Myc, and p53. These new developments in modelling mean that any mutant allele can potentially be turned on or off, or over-or under-expressed, in any tissue at any stage of the life-cycle of the mouse. This will no doubt lead to ever more accurate and powerful mouse models to dissect the genetic pathways that lead to cancer.

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Mutations induced in male germ cells after treatment of transgenic mice with ethylnitrosourea

Cited by 18 publications

References 18 publications

Mutagenicity of Acrylamide and Glycidamide in the Testes of Big Blue Mice

Mutagenicity of Acrylamide and Glycidamide in the Testes of Big Blue Mice

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

New approaches for modelling cancer mechanisms in the mouse

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