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

• Main Authors: van Steeg Harry, van Schooten Frederik J, van Benthem Jan, van Oostrom Conny, Pennings Jeroen LA, Verhofstad Nicole, Godschalk Roger WL
• Format: Article
• Language: English
• Published: BMC 2010-05-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/11/333
• ISSN: 1471-2164

<p>Abstract</p> <p>Background</p> <p>Benzo [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 <it>Xpc</it>^-/-mice than in wild type mice. In this study, we investigated by using microarray technology whether compromised DNA repair in <it>Xpc</it>^-/-mice may lead to a transcriptional reaction of the testis to cope with increased levels of B[a]P induced DNA damage.</p> <p>Results</p> <p>Two-Way ANOVA revealed only 4 genes differentially expressed between wild type and <it>Xpc</it>^-/-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 <it>Xpc</it>^-/-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 <it>Xpc</it>^-/-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.</p> <p>Conclusion</p> <p>Gene expression in testis of untreated <it>Xpc</it>^-/-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.</p>