Gao Xiugong, Yourick Jeffrey J, Topping Vanessa D, Black Thomas, Olejnik Nicholas, Keltner Zachary, Sprando Robert L
Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, MD, USA.
Toxicol Rep. 2014 Dec 19;2:341-350. doi: 10.1016/j.toxrep.2014.12.008. eCollection 2015.
Male and female rats (26-day-old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc) in drinking water for 10 weeks prior to and during mating. Sperm-positive females remained within their dose groups and were exposed to silver acetate during gestation and lactation. At postnatal day 26, the effect of silver ions on the developing F1 generation rat thymus was evaluated at the transcriptional level using whole-genome microarrays. Gene expression profiling analyses identified a dozen differentially expressed genes (DEGs) in each dose group using a loose criterion of fold change (FC) >1.5 and unadjusted < 0.05, regardless of whether the analysis was conducted within each gender group or with both gender groups combined. No dose-dependent effect was observed on the number of DEGs. In addition, none of these genes had a false discovery rate (FDR) <0.05 after correction for multiple testing. These results in combination with the observation that thymus-to-body-weight ratios were not affected and no histopathological abnormalities were identified indicate that exposure to silver ions up to 26.0 mg/kg (equivalent to 40.0 mg/kg silver acetate) did not have an adverse effect on the developing thymus.
在交配前及交配期间,将雄性和雌性大鼠(26日龄)置于含0.0、0.4、4或40毫克/千克体重醋酸银(AgAc)的饮用水中,持续10周。精子呈阳性的雌性大鼠留在各自的剂量组中,并在妊娠和哺乳期接触醋酸银。在出生后第26天,使用全基因组微阵列在转录水平评估银离子对发育中的F1代大鼠胸腺的影响。基因表达谱分析使用宽松的倍数变化(FC)>1.5和未校正的P<0.05标准,在每个剂量组中鉴定出十几个差异表达基因(DEG),无论分析是在每个性别组内进行还是将两个性别组合并进行。未观察到DEG数量的剂量依赖性效应。此外,在进行多重检验校正后,这些基因中没有一个的错误发现率(FDR)<0.05。这些结果与胸腺与体重比值未受影响且未发现组织病理学异常的观察结果相结合,表明暴露于高达26.0毫克/千克(相当于40.0毫克/千克醋酸银)的银离子对发育中的胸腺没有不利影响。