title: Preclinical safety evaluation of IFNalpha2a-NGR.
abstract: 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.
authors.affiliation: Biotechnology Center of The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, People's Republic of China.
authors.forename: Jieru
authors.initials: J
authors.lastname: Meng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Wu
authors.forename: Mingtang
authors.initials: M
authors.lastname: Gao
authors.forename: Wenguang
authors.initials: W
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Hongxing
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001772:Blood Cell Count; D001806:Blood Urea Nitrogen; D001854:Bone Marrow Cells / Q000187:drug effects / Q000648:ultrastructure; D002869:Chromosome Aberrations / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D000882:Haplorhini; D007273:Injections, Intramuscular; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000633:toxicity*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D018482:Muscle, Skeletal / Q000473:pathology; D009152:Mutagenicity Tests; D009842:Oligopeptides / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C526428:NGR peptide; D009842:Oligopeptides; D011994:Recombinant Proteins