Meng Jieru, Yan Zhen, Wu Yongjie, Gao Mingtang, Li Wenguang, Gao Fei, Wang Hongxing, Han Wei, Zhang Yingqi
Biotechnology Center of The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, People's Republic of China.
Regul Toxicol Pharmacol. 2008 Apr;50(3):294-302. doi: 10.1016/j.yrtph.2007.10.014. Epub 2007 Nov 6.
IFNalpha2a-NGR is an antitumor agent of bacterial origin. The report presents the preclinical toxicity studies with IFNalpha2a-NGR in mice, rats and monkeys. The single-dose toxicity study showed no effect on general signs, body weight, food consumption, ophthalmology, hematology and clinical chemistry and necropsy analysis. In repeated-dose toxicity studies, increase in HB was noted both in rat and monkey, showed that IFNalpha2a-NGR may not cause the suppression of hematopoiesis. Decrease in AST, A/G, GLU, T-Bil in rat and AST, TP, GLO in monkey were noted, accompanied by increase in TP and GLB in rat and BUN in monkey. All the clinical chemistry changes were mild, reversible and considered to be incidental, since no related abnormal parameters or results were found. Increase in spleen and thymus organ-to-body weight ratios and decrease in menses were mild, reversible and likely related to pharmacology activity of IFNalpha2a. Ames, chromosomal aberration and bone marrow micronulecus test were conducted and the results were negative. The degree of irritation caused by various concentration of IFNalpha2a-NGR was determined to be the same as that induced by normal saline. In conclusion, preclinical safety studies that IFNalpha2a-NGR was well tolerated at pharmacologically active doses in mice, rats and monkeys.
干扰素α2a-NGR是一种源自细菌的抗肿瘤药物。本报告介绍了干扰素α2a-NGR在小鼠、大鼠和猴子身上的临床前毒性研究。单剂量毒性研究表明，对一般体征、体重、食物消耗、眼科、血液学、临床化学及尸检分析均无影响。在重复剂量毒性研究中，大鼠和猴子的血红蛋白均有升高，表明干扰素α2a-NGR可能不会引起造血抑制。大鼠的谷草转氨酶、白蛋白/球蛋白比值、血糖、总胆红素以及猴子的谷草转氨酶、总蛋白、球蛋白均有降低，同时大鼠的总蛋白和球蛋白以及猴子的尿素氮有所升高。所有临床化学变化均轻微、可逆，且被认为是偶然的，因为未发现相关异常参数或结果。脾脏和胸腺器官与体重比值增加以及月经减少均轻微、可逆，可能与干扰素α2a的药理活性有关。进行了艾姆斯试验、染色体畸变试验和骨髓微核试验，结果均为阴性。不同浓度的干扰素α2a-NGR所引起的刺激程度与生理盐水所致刺激程度相同。总之，临床前安全性研究表明，干扰素α2a-NGR在小鼠、大鼠和猴子体内以药理活性剂量给药时耐受性良好。
