Drug Safety Research Center, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan.
Drug Metab Pharmacokinet. 2012;27(3):307-16. doi: 10.2133/dmpk.dmpk-11-rg-133. Epub 2011 Dec 13.
Cynomolgus macaques, frequently used in drug metabolism studies, are bred mainly in the countries of Asia; however, comparative studies of drug metabolism between cynomolgus macaques bred in these countries have not been conducted. In this study, hepatic gene expression profiles of cynomolgus macaques bred in Cambodia (mfCAM), China (mfCHN), and Indonesia (mfIDN) were analyzed. Microarray analysis revealed that expression of most hepatic genes, including drug-metabolizing enzyme genes, was not substantially different between mfCAM, mfCHN, and mfIDN; only 1.1% and 3.0% of all the gene probes detected differential expression (>2.5-fold) in mfCAM compared with mfCHN and mfIDN, respectively. Quantitative polymerase chain reaction showed that the expression levels of 14 cytochromes P450 (P450s) important for drug metabolism did not differ (>2.5-fold) in mfCAM, mfCHN, and mfIDN, validating the microarray data. In contrast, expression of CYP2B6 and CYP3A4 differed (>2.5-fold, p < 0.05) between cynomolgus (mfCAM, mfCHN, or mfIDN) and rhesus macaques, indicating greater differences in expression of P450 genes between the two lineages. Moreover, metabolic activities measured using 14 P450 substrates did not differ substantially (<1.5-fold) between mfCAM and mfCHN. These results suggest that gene expression profiles, including drug-metabolizing enzyme genes such as P450 genes, are similar in mfCAM, mfCHN, and mfIDN.
食蟹猴常用于药物代谢研究，主要在亚洲国家繁殖；然而，这些国家繁殖的食蟹猴之间的药物代谢比较研究尚未进行。在这项研究中，分析了在柬埔寨（mfCAM）、中国（mfCHN）和印度尼西亚（mfIDN）繁殖的食蟹猴的肝基因表达谱。微阵列分析显示，大多数肝基因的表达，包括药物代谢酶基因，在 mfCAM、mfCHN 和 mfIDN 之间没有显著差异；与 mfCHN 和 mfIDN 相比，仅检测到 1.1%和 3.0%的所有基因探针存在差异表达（>2.5 倍）。定量聚合酶链反应显示，14 种细胞色素 P450（P450s）对于药物代谢很重要，其表达水平在 mfCAM、mfCHN 和 mfIDN 之间没有差异（>2.5 倍），验证了微阵列数据。相比之下，CYP2B6 和 CYP3A4 的表达在食蟹猴（mfCAM、mfCHN 或 mfIDN）和恒河猴之间存在差异（>2.5 倍，p<0.05），表明这两个谱系之间 P450 基因的表达差异更大。此外，使用 14 种 P450 底物测量的代谢活性在 mfCAM 和 mfCHN 之间没有明显差异（<1.5 倍）。这些结果表明，基因表达谱，包括 P450 基因等药物代谢酶基因，在 mfCAM、mfCHN 和 mfIDN 中相似。
