In vivo longitudinal micro-CT study of bent long limb bones in rat offspring

被引:17
作者
De Schaepdrijver, Luc [1 ]
Delille, Peter [1 ]
Geys, Helena [2 ]
Boehringer-Shahidi, Christian [3 ]
Vanhove, Christian [4 ]
机构
[1] Janssen R&D, Preclin Dev & Safety, Beerse, Belgium
[2] Janssen R&D, Biometr & Reporting, Beerse, Belgium
[3] Definiens AG, Munich, Germany
[4] Univ Ghent, Dept Med Image & Signal Proc, B-9000 Ghent, Belgium
关键词
Micro-computed X-ray tomography (micro-CT); Bent long bones; Postnatal skeletal assessment; Non-clinical safety assessment; WAVY RIBS; INDUCTION;
D O I
10.1016/j.reprotox.2014.03.004
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Micro-computed X-ray tomography (micro-CT) has been reported as a reliable method to assess ex vivo rat and rabbit fetal skeletons in embryo-fetal developmental toxicity studies. Since micro-CT is a non-invasive imaging modality it has the potential for longitudinal, in vivo investigation of postnatal skeletal development. This is the first paper using micro-CT to assess the reversibility of drug-induced bent long bones in a longitudinal study from birth to early adulthood in rat offspring. Analysis of the scans obtained on postnatal Day 0, 7, 21 and 80 showed complete recovery or repair of the bent long limb bones (including the scapula) within the first 3 weeks. When assessing risk the ability to demonstrate recovery is highly advantageous when interpreting such transient skeletal change. In summary, in vivo micro-CT of small laboratory animals can aid in non-clinical safety assessment, particularly for specific mechanistic purposes or to address a particular concern in developmental biology. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:91 / 97
页数:7
相关论文
共 24 条
[1]   Interpretation of skeletal variations for human risk assessment: Delayed ossification and wavy ribs [J].
Carney, Edward W. ;
Kimmel, Carole A. .
BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, 2007, 80 (06) :473-496
[2]  
CHAHOUD I, 1991, Teratology, V44, p15A
[3]   A note on the staining of the skeleton of cleared - Specimens with alizarin red S [J].
Dawson, AB .
STAIN TECHNOLOGY, 1926, 1 (04) :123-124
[4]   Osteoblast Recruitment to Sites of Bone Formation in Skeletal Development, Homeostasis, and Regeneration [J].
Dirckx, Naomi ;
Van Hul, Matthias ;
Maes, Christa .
BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS, 2013, 99 (03) :170-191
[5]   Use of magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) in the morphological examination of rat and rabbit fetuses from embryo-fetal development studies [J].
French, Julian ;
Gingles, Neill ;
Stewart, Jane ;
Woodhouse, Neil .
REPRODUCTIVE TOXICOLOGY, 2010, 30 (02) :292-300
[6]  
Guldberg Robert E, 2004, Birth Defects Res C Embryo Today, V72, P250, DOI 10.1002/bdrc.20016
[7]  
Hayasaka I., 1984, CONGENIT ANOM, V24, P111
[8]  
Holmbeck Kenn, 2006, Birth Defects Research, V78, P11, DOI 10.1002/bdrc.20064
[9]  
Khera K S, 1981, Fundam Appl Toxicol, V1, P13
[10]  
KHERA KS, 1978, TOXICOL APPL PHARM, V45, P435, DOI 10.1016/0041-008X(78)90107-2