skip to content
Dovepress - Open Access to Scientific and Medical Research
View our mobile site

8830

A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross

Original Research

(1560) Views  (263) Full article downloads

Authors: Gelinas R, Chesler EJ, Vasconcelos D, Miller DR, Yuan Y, Wang K, Galas D

Published Date July 2011 Volume 2011:4 Pages 35 - 45
DOI: http://dx.doi.org/10.2147/PGPM.S22475

Richard Gelinas1,3, Elissa J Chesler2, Daphne Vasconcelos1, Darla R Miller2, Yue Yuan3, Kai Wang3, David Galas1,3
1Battelle Memorial Institute, Columbus, OH; 2Oak Ridge National Laboratory, Oak Ridge, TN; 3Institute for Systems Biology, Seattle, WA, USA

Abstract: The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs) were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain.

Keywords: collaborative cross, drug side effects, genetic diversity, disease susceptibility, disease resistance, bleomycin, lung disease






Readers of this article also read:

Pharmacogenomic application of the haptoglobin genotype in the treatment of HDL dysfunction
Pharmacogenomics in osteoporosis: Steps toward personalized medicine
Ego mechanisms of defense are associated with patients’ preference of treatment modality independent of psychological distress in end-stage renal disease
Can a gentamicin-specific chart reduce neonatal medication errors?
Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered
Dashboards in neonatology
ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer
Clinical implementation of RNA signatures for pharmacogenomic decision-making
Role of cytochrome P450 genotype in the steps toward personalized drug therapy
The role of genetics in pre-eclampsia and potential pharmacogenomic interventions