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Induction of somatic intrachromosomal recombination inversion events by cyclophosphamide in a transgenic mouse model

Authors :
Pamela J. Sykes
Alexander A. Morley
Antony M. Hooker
Andrew Jacobs
Linda Kingsbury
Carolyn S Harrington
Source :
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 397:209-219
Publication Year :
1998
Publisher :
Elsevier BV, 1998.

Abstract

Somatic intrachromosomal recombination (SICR) can result in chromosomal inversion and deletion, mechanisms which are important in carcinogenesis. We have utilised a transgenic mouse model to study SICR inversion events in spleen cells. The transgenic construct is designed so that expression of an Escherichia coli lacZ transgene only occurs in a cell when an SICR inversion event occurs in the region of the transgene. The inversion events can then be detected by histochemical staining of frozen spleen sections for transgene expression and by polymerase chain reaction across the inversion breakpoints. The spontaneous inversion frequency in spleen rose 2-fold from 1.54 +/- 0.24 x 10(-4) (mean +/- SE) in 4-month-old transgenic mice to 3.12 +/- 0.67 x 10(-4) in 22-month-old mice. Four- or 8-month-old mice were treated with a single intraperitoneal injection of cyclophosphamide, with doses ranging from 0.01 to 100 mg/kg. The animals were killed 3 days after treatment. A significant induction of SICR inversions was detected at all doses with a 3.2-fold maximum induction of inversions detected at 10 mg/kg. These results suggest that the transgenic mouse model used here may be a sensitive model for studying the role of SICR in mutation and in studying risk assessment of environmental DNA-damaging agents.

Details

ISSN :
00275107
Volume :
397
Database :
OpenAIRE
Journal :
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
Accession number :
edsair.doi.dedup.....a46a25b64b21c3e9650a4be4134df446
Full Text :
https://doi.org/10.1016/s0027-5107(97)00213-3