Department of Health Risk Analysis and Toxicology, School for Nutrition, Toxicology and Metabolism, Maastricht University, PO box 616, 6200 MD Maastricht, the Netherlands.
BMC Genomics. 2010 May 26;11:333. doi: 10.1186/1471-2164-11-333.
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.
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.
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.
苯并[a]芘（B[a]P）暴露会在精子发生和睾丸的各个阶段诱导 DNA 加合物，并且在核苷酸切除修复缺陷的 Xpc-/- 小鼠中，这些损伤的清除效率低于野生型小鼠。在这项研究中，我们通过使用微阵列技术研究了 Xpc-/- 小鼠中受损的 DNA 修复是否会导致睾丸发生转录反应，以应对 B[a]P 诱导的 DNA 损伤水平的增加。
双向方差分析仅显示出野生型和 Xpc-/- 小鼠之间有 4 个基因差异表达，而无论小鼠基因型如何，B[a]P 处理和未处理的睾丸之间有 984 个基因差异表达。然而，这些 B[a]P 调节基因的表达水平在 Wt 和 Xpc-/- 小鼠之间存在差异（p = 0.000000141），并且主要参与细胞周期、翻译、染色质结构和精子发生的调节，表明存在普遍的应激反应。此外，细胞周期相依赖基因表达分析表明，在两种基因型中，B[a]P 暴露后参与 G1-S 和 G2-M 期阻滞的基因表达增加。在 Xpc-/- 小鼠中，G2-M 检查点的平均基因表达诱导略有增加，但未达到统计学意义（P = 0.086）。其他预期通过暴露而改变的过程，如细胞凋亡和 DNA 修复，在基因表达水平上没有发现被调节。
未处理的 Xpc-/- 和野生型小鼠睾丸中的基因表达非常相似，仅有 4 个基因差异表达。暴露于苯并[a]芘会影响两种基因型中参与细胞周期调节的基因的表达，表明睾丸中未修复的 DNA 损伤的存在会阻止细胞增殖，以保护两种 DNA 修复能力正常和缺陷的动物的 DNA 完整性。
