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Environmental exposure of the mouse germ line: DNA adducts in spermatozoa and formation of De Novo mutations during spermatogenesis

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posted on 24.10.2012, 09:00 by A-K. Olsen, Å. Andreassen, R. Wiger, N. Duale, G. Brunborg, Rajinder Singh, Peter B. Farmer
Background Spermatozoal DNA damage is associated with poor sperm quality, disturbed embryonic development and early embryonic loss, and some genetic diseases originate from paternal de novo mutations. We previously reported poor repair of bulky DNA-lesions in rodent testicular cells. Methodology/Principal Findings We studied the fate of DNA lesions in the male germ line. B[a]PDE-N2-dG adducts were determined by liquid chromatography-tandem mass spectrometry, and de novo mutations were measured in the cII-transgene, in Big Blue®mice exposed to benzo[a]pyrene (B[a]P; 3×50 mg/kg bw, i.p.). Spermatozoa were harvested at various time-points following exposure, to study the consequences of exposure during the different stages of spermatogenesis. B[a]PDE-N2-dG adducts induced by exposure of spermatocytes or later stages of spermatogenesis persisted at high levels in the resulting spermatozoa. Spermatozoa originating from exposed spermatogonia did not contain DNA adducts; however de novo mutations had been induced (p = 0.029), specifically GC-TA transversions, characteristic of B[a]P mutagenesis. Moreover, a specific spectrum of spontaneous mutations was consistently observed in spermatozoa. Conclusions/Significance A temporal pattern of genotoxic consequences following exposure was identified, with an initial increase in DNA adduct levels in spermatozoa, believed to influence fertility, followed by induction of germ line de novo mutations with possible consequences for the offspring.

Funding

This work was supported by The Research Council of Norway [148703 to AKO], and by Environmental Cancer Risk, Nutrition and Individual Susceptibility, a European Union Network of Excellence (ECNIS, Contract No. FOOD-CT-2005-513943, to RS and PBF).

History

Citation

PLoS ONE, 2010, 5 (6)

Published in

PLoS ONE

Publisher

Public Library of Science

issn

1932-6203

eissn

1932-6203

Copyright date

2010

Available date

24/10/2012

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011349

Language

en

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