Comparison of radiation- and chemically-induced dominant lethal mutations in male mice

Ehling, U.H.

doi:10.1016/0027-5107(71)90030-3

Cited by 129 publications

(22 citation statements)

References 17 publications

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“…For induction of germline mutation by IR, however, spermatogonia in adult testes were found less susceptible than pachytene spermatocytes and spermatids in indirect germline mutation assays [24][25][26]38,39]. In these germline mutation assays, germline mutation is assessed in offspring of IR-treated male mice.…”

Section: Discussionmentioning

confidence: 99%

“…For example, aspermia was observed in male patients with Hodgkin's disease after receiving lower trunk fractionated irradiation therapy [23]. Further, spermatids are susceptible to IR-induced mutations using the SL test [24], dominant lethal assay [25] and ESTRs [26]. However, to date, IR-induced cell type dependent germline mutant frequencies were deduced largely from the mutant frequency in the offspring of exposed mice [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

“…Further, spermatids are susceptible to IR-induced mutations using the SL test [24], dominant lethal assay [25] and ESTRs [26]. However, to date, IR-induced cell type dependent germline mutant frequencies were deduced largely from the mutant frequency in the offspring of exposed mice [24][25][26]. By directly measuring mutant frequency in spermatogenic cells in Lac I transgenic mice, our laboratory has found that different spermatogenic cell types have different spontaneous mutant frequencies with the highest among the tested cell types being detected in primitive type A spermatogonia [27].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Post-meiotic stages of gametogenesis were the most sensitive to the induction of damage by cyclophosphamide [34]. Ehling [35] treated mice with three doses of mitomycin C and obtained different time-response curves for each one. Germ cells at later phases of spermatogenesis were affected only at the highest dose: 7.0 mg/kg b.w.…”

Section: Discussionmentioning

confidence: 99%

Establishment of the dominant lethal test in the freshwater mollusk Biomphalaria glabrata (Say, 1818)

Nakano

Watanabe

Ohlweiler

et al. 2003

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Mutagens in the environment may represent a long-term risk for ecosystems. The reproductive potential of populations can be affected by alterations in the fecundity and offspring viability caused by germ cell mutations. Despite the ecological relevance of these effects, there are few studies on germ cell mutagenicity in natural populations. Biomphalaria glabrata was chosen for this study because of the scarcity of data on freshwater invertebrates and the ecological importance of this group. The aim of this study was to establish a germ cell mutagenicity test in B. glabrata by using a similar approach to that used in the dominant lethal test in rodents. Mitomycin C was used as a direct mutagen and cyclophosphamide as a mutagen that requires metabolic activation. Wild-type snails were exposed for 10 days to three concentrations of each agent and crossed with non-exposed albino snails at the end of the treatment. The total frequencies of malformations were analyzed in the offspring of wild-type snails; among the offspring of albino snails, only the heterozygous wild-type embryos were analyzed for malformations. Both agents induced germ cell mutations. The analysis of the offspring of the wild-type snails showed an effect of the exposure up to approximately 5 days after the end of the treatment with cyclophosphamide; the effect of mitomycin C was observed until 45 days after the end of the exposure. There was an increase in the frequencies of malformations in the wild-type offspring of the non-exposed albino snails crossed with the wild-type snails exposed to both agents. The dominant lethal test in B. glabrata proposed in this work is easy to perform, efficient, specific and sensitive in the evaluation of germ cell mutations induced by reference mutagens. The possibility of expanding its use to environmental biomonitoring studies seems very promising and worth trying.

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“…In general, chemically-induced dominant lethal mutations show stage-specific effects in mammalian spermatogenesis. Ehling (1971) demonstrated that MC induced dominant lethal mutations in early spermatids and spermatocytes, but had no effect on late spermatids or spermatozoa of male mice. This induction of dominant lethal mutations by MC in early spermatids shows a striking difference in stage specificity from those induced by some other alkylating agents in late spermatids and spermatozoa.…”

Section: Introductionmentioning

confidence: 98%

Chromosome aberrations induced by mitomycin c treatment in early spermatids of male mice.

Katoh

Tanaka

Iwahara

1981

The Japanese journal of genetics

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Evidence that MC-induced dominant lethal mutations in early spermatids are attributable to chromosome aberrations was obtained through cytogenetic analysis of first-cleavage metaphases.Male mice were intravenously injected with 5 mg/kg of mitomycin C (MC). These males were serially mated with females during 6 weeks after treatment.Chromosome slides were prepared from eggs collected from the ampulla. The maximum frequencies of chromosome aberrations in male pronuclei in the eggs were obtained in early spermatid stages. A close correlation between the frequency of eggs with chromosome aberrations and that of dominant lethal mutations at the same dose was observed.

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Comparison of radiation- and chemically-induced dominant lethal mutations in male mice

Cited by 129 publications

References 17 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

Establishment of the dominant lethal test in the freshwater mollusk Biomphalaria glabrata (Say, 1818)

Chromosome aberrations induced by mitomycin c treatment in early spermatids of male mice.

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