Transcriptional profiling of the hippocampus of MutaTMMouse treated with benzo[a]pyrene. Mus musculus strain:Muta(tm)Mouse

Benzo[a]pyrene (BaP) is a genotoxic carcinogen and a neurotoxicant. The neurotoxicity of BaP is proposed to arise from either genotoxicity leading to neuronal cell death, or perturbed expression of N-methyl-D-aspartate receptor (NMDAR) subunits. To explore these hypotheses, we profiled hippocampal gene expression of adult male MutaTMMouse administered 1, 35, or 70 mg BaP/kg bw per day by oral gavage for three days, by RNA-Sequencing (RNA-Seq), DNA microarrays, and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) 24 hr post-exposure. RNA-Seq revealed altered expression of zero, 260, and 219 genes (p-value = ± 1.5) following exposure to the low, medium, and high doses, respectively; 54 genes were confirmed using microarrays.

苯并[a]芘（Benzo[a]pyrene, BaP）是一种遗传毒性致癌物，同时也是神经毒物。现有研究提出，BaP的神经毒性可能源于两类机制：一是通过遗传毒性引发神经元细胞死亡，二是扰动N-甲基-D-天冬氨酸受体（N-methyl-D-aspartate receptor, NMDAR）亚基的表达。为探究上述假说，本研究对经每日以1、35或70 mg BaP/kg体重剂量灌胃染毒3天的成年雄性MutaTM小鼠，于暴露后24小时采用RNA测序（RNA-Seq）、DNA微阵列及实时定量反转录聚合酶链式反应（RT-PCR）对其海马基因表达谱进行检测。RNA-Seq结果显示，低、中、高剂量暴露组分别有0、260、219个基因的表达出现显著变化（p值=±1.5）；其中54个基因的表达变化通过DNA微阵列得到验证。