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


RESULTS
Two-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.


CONCLUSIONS
Gene 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.
Verhofstad
Nicole
N
Department of Health Risk Analysis and Toxicology, School for Nutrition, Toxicology and Metabolism, Maastricht University, PO box 616, 6200 MD Maastricht, the Netherlands.
Pennings
Jeroen L A
JL
van Oostrom
Conny Th M
CT
van Benthem
Jan
J
van Schooten
Frederik J
FJ
van Steeg
Harry
H
Godschalk
Roger W L
RW
D000220:Adaptation, Biological / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D013737:Testis / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors
D004268:DNA-Binding Proteins; C501002:Xpc protein, mouse; D001564:Benzo(a)pyrene