Vidal Justin D, Drobatz Lita S, Holliday Denise F, Geiger Lee E, Thomas Heath C
GlaxoSmithKline, King of Prussia, PA 19406-0939, USA.
Toxicol Pathol. 2010 Feb;38(2):297-302. doi: 10.1177/0192623309358906. Epub 2010 Feb 2.
The cynomolgus macaque is the most commonly used nonhuman primate in nonclinical toxicity testing, but the impact of the geographic source of cynomolgus macaque on differences in spontaneous pathology and response to xenobiotics has only recently been explored. Previous work from the authors' facility has described spontaneous cardiac findings in predominantly Indonesian-source animals; however, the authors have recently observed a novel spectrum of cardiac findings in Mauritian-source animals. This review evaluated the spontaneous macroscopic and microscopic cardiac findings in vehicle control Mauritian-source macaques used for routine toxicity testing. When compared to the prior review in predominantly Indonesian macaques, a higher incidence of myocardial degeneration was observed with additional novel findings including macroscopic and microscopic subendocardial hemorrhage with hemosiderin, myocardial fibrosis, and arterial medial degeneration/hemorrhage. Other findings including inflammatory cell infiltrates, anisokaryosis, and squamous plaques were observed with a comparable incidence as previously reported in Indonesian macaques. Myocardial degeneration, subendocardial hemorrhage, and myocardial fibrosis can mimic test-article-related cardiac toxicity, and a thorough understanding of the incidence and severity of these spontaneous findings is necessary to prevent misidentifying test-article-related cardiac findings in this genetic source of cynomolgus macaque in nonclinical safety testing.
食蟹猕猴是非临床毒性试验中最常用的非人类灵长类动物,但食蟹猕猴的地理来源对自发病理变化和对外源生物反应差异的影响直到最近才被研究。作者所在机构之前的研究描述了主要来自印度尼西亚的动物的自发性心脏病变;然而,作者最近在来自毛里求斯的动物中观察到了一系列新的心脏病变。本综述评估了用于常规毒性试验的毛里求斯来源食蟹猕猴载体对照组的自发性大体和微观心脏病变。与之前对主要为印度尼西亚食蟹猕猴的综述相比,观察到心肌变性的发生率更高,还有其他新发现,包括大体和微观层面的心内膜下出血伴含铁血黄素、心肌纤维化以及动脉中层变性/出血。还观察到其他病变,包括炎性细胞浸润、核大小不均和鳞状斑块,其发生率与之前报道的印度尼西亚食蟹猕猴相当。心肌变性、心内膜下出血和心肌纤维化可能会模拟与受试物相关的心脏毒性,因此,全面了解这些自发病变的发生率和严重程度对于在非临床安全性试验中防止误判这种遗传来源的食蟹猕猴中与受试物相关的心脏病变至关重要。