The infant mouse as a in vivo model for the detection and study of DNA damage–induced changes in the liver

✍ Scribed by Randall Reynolds; Sam Witherspoon; Tony Fox

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 239 KB
• Volume: 40
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20017

✦ Synopsis

Abstract

The present work describes the use of the infant (4‐wk‐old) mouse as an animal model for the study of DNA damage–induced G~1~ checkpoint response, changes in p53 protein levels, and multiple gene expression changes after DNA damage has been induced in the liver. Hepatocytes in the infant B6C3F1 mouse had a proliferation index that was 27 times greater than that of the 12‐wk‐old B6C3F1 mouse (57.4 vs. 2.1%, respectively). Eight hours after infant mice were exposed to the DNA damaging agents bleomycin (100 mg/kg, i.p.) or 10 Gy of whole body gamma irradiation, the G~1~/S ratio significantly increased from 21 (control) to 66 and 75, respectively, because of the induction of the G~1~/S checkpoint response. One hour after whole body irradiation of infant mice the levels of the p53 protein, phosphoserine 18‐p53 and phosphoserine 23‐p53 increased dramatically and tended to peak at 1 h in the liver, whereas the p21^WAF1^ protein increased more slowly and tended to peak at 2 h after irradiation. The mRNA expression of the p53‐response genes p21, murine double minute clone 2 (mdm2), and cyclin G was increased at 2 h after irradiation but was decreased by 8 h postirradiation, relative to the 2‐h time‐point. The expression of insulin‐like growth factor binding protein‐1 (IGFBP‐1) and growth‐regulated oncogene 1 (GRO1) increased at 2 and 8 h postirradiation. This work characterizes various parameters in the infant mouse, thus validating the use of this model to study in vivo DNA damage–induced cell‐cycle–related changes. © 2004 Wiley‐Liss, Inc.