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Favor, J. ; Sund, M. ; Neuhäuser-Klaus, A. ; Ehling, U.H.

A dose-response analysis of ethylnitrosourea-induced recessive specific-locus mutations in treated spermatogonia of the mouse.

Mutat. Res. -Fund. Mol. Mech. Mutag. 231, 47-54 (1990)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
A dose-response analysis was carried out with 2 independent data sets available for ethylnitrosourea-induced specific-locus mutations in spermatogonia of the mouse. It was assumed that the occurence of mutation is binomially distributed and maximum-likelihood procedures were employed to determine the appropriateness of 4 alternative models, Linear, Linear-Quadratic, Power, and Threshold, in describing the dependence of the binomial parameter on dose. For both data sets, the Threshold model yielded a far superior fit and the threshold dose was estimated to be between 34 and 39 mg/kg. These results are supported by the relatively inefficient response of ethylnitrosourea at lower doses in inducing DNA adducts. Relevant specific-locus mutation results in the mouse for low-dose fractionated treatment as well as the recovery of mutation mosaics indicate the threshold model to be an oversimplification. Rather than a threshold dose below which 100% of the induced DNA adducts are repaired, we propose that some DNA adducts which may eventually be fixed as a mutation persist through a number of repair-competent cell divisions and do not interfere with normal cell function nor do they induce a repair response before being eventually fixed as a mutation. We interpret the threshold response for ethylnitrosourea-induced specific-locus mutations to be due to a saturable repair process which at lower doses results in ethylnitrosourea being less efficient in inducing mutation. Once this repair process is saturated, a clear dose-related increase in the mutation rate is observed.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords (mouse) ; Dose-response Analysis ; Ethylnitrosourea ; Specific-locus Mutations ; Threshold
ISSN (print) / ISBN 0027-5107
e-ISSN 1873-135X
Journal Mutation Research / Fundamental and Molecular Mechanisms of Mutagenesis
Quellenangaben Volume: 231, Issue: 1, Pages: 47-54 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institut für Säugetiergenetik