Benzo(a)pyrene induces similar gene expression changes in testis of DNA repair proficient and deficient mice

BMC Genomics

Research Article

Roger WL Godschalk¹  Nicole Verhofstad¹  Frederik J van Schooten¹  Conny ThM van Oostrom²  Jan van Benthem²  Harry van Steeg²  Jeroen LA Pennings² 

[1] Department of Health Risk Analysis and Toxicology, School for Nutrition, Toxicology and Metabolism, Maastricht University, PO box 616, 6200, Maastricht, MD, the Netherlands;Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), PO box 1, 3720, Bilthoven, BA, the Netherlands;

关键词: Gene Ontology;    Nucleotide Excision Repair;    Cell Cycle Phase;    Average Gene Expression;    Spermatogonial Stem Cell;   

DOI  :  10.1186/1471-2164-11-333

 received in 2009-09-18, accepted in 2010-05-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundBenzo [a]pyrene (B[a]P) exposure induces DNA adducts at all stages of spermatogenesis and in testis, and removal of these lesions is less efficient in nucleotide excision repair deficient Xpc-/- mice than in wild type mice. In this study, we investigated by using microarray technology whether compromised DNA repair in Xpc-/- mice may lead to a transcriptional reaction of the testis to cope with increased levels of B[a]P induced DNA damage.ResultsTwo-Way ANOVA revealed only 4 genes differentially expressed between wild type and Xpc-/- mice, and 984 genes between testes of B[a]P treated and untreated mice irrespective of the mouse genotype. However, the level in which these B[a]P regulated genes are expressed differs between Wt and Xpc-/- mice (p = 0.000000141), and were predominantly involved in the regulation of cell cycle, translation, chromatin structure and spermatogenesis, indicating a general stress response. In addition, analysis of cell cycle phase dependent gene expression revealed that expression of genes involved in G1-S and G2-M phase arrest was increased after B[a]P exposure in both genotypes. A slightly higher induction of average gene expression was observed at the G2-M checkpoint in Xpc-/- mice, but this did not reach statistical significance (P = 0.086). Other processes that were expected to have changed by exposure, like apoptosis and DNA repair, were not found to be modulated at the level of gene expression.ConclusionGene expression in testis of untreated Xpc-/- and wild type mice were very similar, with only 4 genes differentially expressed. Exposure to benzo(a)pyrene affected the expression of genes that are involved in cell cycle regulation in both genotypes, indicating that the presence of unrepaired DNA damage in testis blocks cell proliferation to protect DNA integrity in both DNA repair proficient and deficient animals.

【 授权许可】

Unknown   
© Verhofstad et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.