Developmental response of zygotes exposed to similar mutagens

W. M. Generoso, A. G. Shourbaji, Walter W Piegorsch, J. B. Bishop

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Exposure of mouse zygotes to ethylene oxide (EtO) or ethyl methanesulfonate (EMS) led to high incidences of fetal death and of certain classes of fetal malformations (Generoso et al., 1987, 1988; Rutledge and Generoso, 1989). These effects were not associated with induced chromosomal aberrations (Katoh et al., 1989) nor are they likely to be caused by gene mutations (Generoso et al., 1990). Nevertheless, the anomalies observed in these studies resemble the large class of stillbirths and sporadic defects in humans that are of unknown etiology, such as cleft palate, omphalocoel, clubfoot, hydrops and stillbirths (Czeizel, 1985; Oakley, 1986). Therefore, we continue to study the possible mechanisms relating to induction of these types of zygote-derived anomalies in mice. Effects of zygote exposure to the compounds methyl methanesulfonate (MMS), dimethyl sulfate (DMS), and diethyl sulfate (DES), which have similar DNA-binding properties as EtO and EMS, were studied. DMS and DES, but not MMS, induced effects that are similar to those induced by EtO and EMS. Thus, no site-specific alkylation product was identifiable as the critical target for these zygote-derived anomalies. We speculate that the developmental anomalies arose as a result of altered programming of gene expression during embryogenesis.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume250
Issue number1-2
DOIs
StatePublished - 1991
Externally publishedYes

Fingerprint

Zygote
Mutagens
Ethyl Methanesulfonate
Ethylene Oxide
Methyl Methanesulfonate
Stillbirth
Clubfoot
Fetal Death
Alkylation
Cleft Palate
Chromosome Aberrations
Embryonic Development
Edema
Gene Expression
Mutation
DNA
Incidence
Genes
diethyl sulfate
dimethyl sulfate

Keywords

  • Diethyl sulphate
  • Dimethyl sulphate
  • Foetal anomalies
  • Methyl methanesulphonate
  • Zygotes

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis

Cite this

Developmental response of zygotes exposed to similar mutagens. / Generoso, W. M.; Shourbaji, A. G.; Piegorsch, Walter W; Bishop, J. B.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 250, No. 1-2, 1991, p. 439-446.

Research output: Contribution to journalArticle

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