Dose-dependent induction of recessive mutations with N-ethyl-N-nitrosourea in primordial germ cells of male mice

Shibuya, Tohru; Horiya, N.; Matsuda, Hiroshi; Sakamoto, Kyoko; Hara, Takumi

doi:10.1016/0027-5107(96)00108-x

Cited by 12 publications

(8 citation statements)

References 14 publications

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“…Pregnant inbred female mice or rats are administered with test substances; the adminis-tration should be at the speciˆc embryonic stage and should be once. Therefore, the targets of this toxicological study are embryonic somatic cells and PGC (31,34,35). Mating with females or males from control and animals treated at embryonic stage must be continued for 2 generations.…”

Section: Proposed Embryo-originated Epigenetic Toxicology Methodsmentioning

confidence: 99%

“…Furthermore, this method is designed to check whether chemical substances have a TG eŠect. The method was designed mainly according to the achievements of Skinner's group (31) and Shibuya et al (32)(33)(34)(35).…”

Section: Epigenetic Toxicologymentioning

confidence: 99%

“…Mutagenesis and intragenic recombination by the potent ethylating agent ENU in male PGC were examined by Shibuya et al (33)(34)(35). Mutation frequencies of PGC in SLT were in stage-and dose-dependent manners using ENU.…”

Section: Introduction To Epigenetic Toxicologymentioning

confidence: 99%

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Introduction to Epigenetic Toxicology of Chemical Substances

Shibuya¹,

Horiya²

2011

Genes and Environment

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Epigenetics (EG) is a highly regulated biochemical mechanism underlying the expression of genes related to development and cellular diŠerentiation that is disrupted by environmental stressors including chemicals and radiation. Studies of these phenomena are known as environmental epigenetics (EEG). Regulation of gene expression by the epigenetic mechanism is deeply involved in the developmental stages of animals and humans. EEG is, therefore, very important in theˆeld of toxicology because it deals with the state of gene expression in all types of somatic and germ cells disrupted by environmental chemicals. We propose here an``Embryo-originated Epigenetic Toxicology Method (EEGT)''. In this method embryonic somatic and germ cells are treated with test substances and various toxicological phenomena in whole bodies are examined. Observations on transgenerational eŠects are also important in this method. This new method could unite various toxicological phenomena based on EEG.

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Section: Proposed Embryo-originated Epigenetic Toxicology Methodsmentioning

confidence: 99%

Section: Epigenetic Toxicologymentioning

confidence: 99%

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Introduction to Epigenetic Toxicology of Chemical Substances

Shibuya¹,

Horiya²

2011

Genes and Environment

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“…Establishment of the primordial germ cell lineage occurs early during development; in the mouse on GD 8, 10-100 primordial germ cells can be identified; primordial germ cells replicate by mitosis so that their numbers depend on mitotic activity. In mice, in utero exposure of male fetuses to a toxicant such as N-ethyl-Nnitrosourea induced a high rate of recessive mutations in the primordial germ cells of male progeny (Shibuya et al, 1996). Spermatogonia undergo several mitotic cell divisions (5 in the rat) in the adult testis to become spermatocytes, which then undergo 2 meiotic cell divisions to form spermatids (spermacytogenesis).…”

Section: Evidence From Animal Modelsmentioning

confidence: 99%

Paternal Exposure to Drugs and Environmental Chemicals: Effects on Progeny Outcome

Hales

Robaire

2001

Journal of Andrology

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“…With the treatment schedule used in our study, primordial germ cells (PGCs) were exposed to estrogenic drugs. Critical evidence for the susceptibility of mouse PGCs to genetic damage was reported by Shibuya and co-workers (12,13). They treated transplacentally C3H/He mice with varying doses of ethylnitrosourea (ENU) on gestational day 8.5, 10.5 or 13.5 and examined the incidence of recessive visible mutations at six speciˆc-loci in F1 of a cross of the treated males×tester females from the PW strain.…”

Section: Introductionmentioning

confidence: 99%