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Zeeland, A.A. van ; de Groot, A. ; Neuhäuser-Klaus, A.

DNA Adduct Formation in Mouse Testis by Ethylating Agents. A Comparison with Germ Cell Mutagenesis.

Mutat. Res. -Fund. Mol. Mech. Mutag. 231, 55-62 (1990)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
DNA adduct formation in various organs of mice was determined after i.p. injection with the ethylating agents N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate (EMS), and diethyl sulfate (DES). The potency of the 3 chemicals to react either at the O6 position of guanine or at the N-7 position of guanine was related to their potency to induce mutations in the specific-locus assay of the mouse. ENU, which produces relatively high levels of O-alkylations (O6-ethylguanine), is primarily mutagenic in spermatogonia of the mouse, whereas EMS and DES, which produce relatively high levels of N-alkylations (7-ethylguanine) in DNA, are much more mutagenic in post-meiotic stages of male germ cells. The relationship between exposure to ENU and the dose, determined as O6-ethylguanine per nucleotide in testicular DNA, is non-linear. However, the relationship between dose and mutation induction in spermatogonia by ENU appears to be linear, which is expected if O6-ethylguanine is the major mutagenic lesion. The relatively high mutagenic potency of EMS and DES in the late stages of spermatogenesis is probably due to the accumulation of apurinic sites which generate mutations after fertilization. A comparison of mutation induction by ENU in spermatogonia and mutation induction in cultured mammalian cells indicates that about 10 O6-ethylguanine residues were necessary in the coding region of a gene to generate a mutation.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords DNA adducts; Ethylating agents; Germ-cell mutagenesis
ISSN (print) / ISBN 0027-5107
e-ISSN 1873-135X
Journal Mutation Research / Fundamental and Molecular Mechanisms of Mutagenesis
Quellenangaben Volume: 231, Issue: 1, Pages: 55-62 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)