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Title: Developmental anomalies: Mutational consequence of mouse zygote exposure

Abstract

One of the objectives of mutagenesis research in mice is to enrich our knowledge of basic mammalian biology. The practical goal is to apply this knowledge to the problems of human health. The research described here exemplifies this philosophy. The observation that certain mutagens induced high incidences of fetal anomalies and death following exposure during the zygote stage is a new phenomenon in mutagenesis and experimental embryopathy. The mechanism for the induction of zygote-derived anomalies appears to be genetic, but it is not of the conventional type. These zygote-derived anomalies resemble the large class of stillbirths and sporadic defects in humans that are of unknown etiology. The zygote research in mice presents an opportunity for studying the molecular and cellular pathogenesis of this class of defects. 12 refs., 1 fig., 3 tabs.

Authors:
 [1];  [2];  [3]
  1. (Oak Ridge National Lab., TN (USA))
  2. (Children's Hospital and Medical Center, Seattle, WA (USA). Dept. of Labs.)
  3. (Wistar Inst. of Anatomy and Biology, Philadelphia, PA (USA))
Publication Date:
Research Org.:
Oak Ridge National Lab., TN (USA)
Sponsoring Org.:
DOE/ER; DOHHS
OSTI Identifier:
5046846
Report Number(s):
CONF-8911146-3
ON: DE90005282; CNN: Y01-ES-20085
DOE Contract Number:
AC05-84OR21400
Resource Type:
Conference
Resource Relation:
Conference: Banbury Center conference on mutation induction and heritability in mammalian germ cells, Cold Spring Harbor, NY (USA), 12-15 Nov 1989
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; MICE; CONGENITAL MALFORMATIONS; ZYGOTES; SENSITIVITY; CHROMOSOMAL ABERRATIONS; DOMINANT MUTATIONS; EVALUATION; GENETICS; HEREDITARY DISEASES; LETHAL MUTATIONS; MORTALITY; MUTAGENESIS; MUTAGENS; MUTATION FREQUENCY; PRENATAL EXPOSURE; TERATOGENESIS; ANIMALS; BIOLOGY; DISEASES; MALFORMATIONS; MAMMALS; MUTATIONS; PATHOLOGICAL CHANGES; RODENTS; VERTEBRATES; 550200* - Biochemistry; 560300 - Chemicals Metabolism & Toxicology

Citation Formats

Generoso, W.M., Rutledge, J.C., and Aronson, J.. Developmental anomalies: Mutational consequence of mouse zygote exposure. United States: N. p., 1989. Web.
Generoso, W.M., Rutledge, J.C., & Aronson, J.. Developmental anomalies: Mutational consequence of mouse zygote exposure. United States.
Generoso, W.M., Rutledge, J.C., and Aronson, J.. Sun . "Developmental anomalies: Mutational consequence of mouse zygote exposure". United States. doi:.
@article{osti_5046846,
title = {Developmental anomalies: Mutational consequence of mouse zygote exposure},
author = {Generoso, W.M. and Rutledge, J.C. and Aronson, J.},
abstractNote = {One of the objectives of mutagenesis research in mice is to enrich our knowledge of basic mammalian biology. The practical goal is to apply this knowledge to the problems of human health. The research described here exemplifies this philosophy. The observation that certain mutagens induced high incidences of fetal anomalies and death following exposure during the zygote stage is a new phenomenon in mutagenesis and experimental embryopathy. The mechanism for the induction of zygote-derived anomalies appears to be genetic, but it is not of the conventional type. These zygote-derived anomalies resemble the large class of stillbirths and sporadic defects in humans that are of unknown etiology. The zygote research in mice presents an opportunity for studying the molecular and cellular pathogenesis of this class of defects. 12 refs., 1 fig., 3 tabs.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 1989},
month = {Sun Jan 01 00:00:00 EST 1989}
}

Conference:
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  • There are many chemicals to which certain groups of humans are exposed and for which induction of transmissible mutations in mice has been demonstrated. Assessment of genetic risk to humans from these environmental mutagens requires accurate identification and quantification in experimental systems of the types of mutagenic damage that they can produce in the germ line and which can be transmitted to the conceptuses. Conventionally the types of genetic damage considered in this process are gene mutations (dominant, semidominant, and recessive), small deficiencies, structural chromosomal anomalies (reciprocal translocations, inversions, duplications, etc.), and numerical chromosomal anomalies (whole chromosomes missing or inmore » excess). This report presents yet another type of mutagenic response, albeit its nature is still unknown. 13 refs.« less
  • The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals.
  • For a given spermatozoon participating in conception, only a relatively short period of its cell lineage has been spent in poststem-cell stages of spermatogenesis. For this reason, the male genome participating in formation of the conceptus is less likely to have been exposed to mutagens during poststem-cell stages than during spermatogonial stem-cell of earlier stages. Nevertheless, in addressing questions of genetic hazard, the later stages cannot be ignored and may even represent a significant part of the risk if, as is already known for some mutagens, these cell types are disproportionally sensitive. Furthermore, the poststem-cell stages, which vary considerably amongstmore » themselves in their array of chromosome and chromatin configurations, offer biological materials that are potentially useful in addressing questions of mutagenic mechanisms. 22 refs., 4 tabs.« less
  • Gravid female mice received either a single subcutaneous dose of cerium citrate (80 mg Ce/kg) or an equivalent (in citrate) dose of sodium citrate on day 7 or 12 of gestation or on day 2 postpartum. To separate effects of prenatal and postnatal exposure, a cross-fostering design was employed. The weight and gross activity of the neonates were assessed on day 8 or 13 postpartum. Open-field behavioral parameters, accelerating rotarod performance, and passive avoidance learning were assessed on day 60-65 postpartum. Maternal offspring retrival latency was measured on day 3 postpartum. Maternal offspring retrieval latency was measured on day 3more » postpartum. Analyses revealed that neonatal weight was reduced both in offspring exposed to Ce in utero and in the offspring of mothers receiving Ce during lactation/suckling. Ce also appeared to affect maternal/offspring interaction: pups exposed prenatally to Ce were retrieved in less time than control pups. Except for an increased frequency of rearings in the open field of adult offspring exposed to Ce in utero, Ce exposure had no apparent effect on behavioral parameters, either in neonatal or adult offspring.« less