title: Inversion due to intrachromosomal recombination produced by carcinogens in a transgenic mouse model.
abstract: Somatic intrachromosomal recombination (SICR) can result in inversions and deletions in the DNA. pKZ1 mice possess an Escherichia coli (E. coli) lacZ transgene which is only expressed after a DNA inversion involving the transgene occurs. The E. coli beta-galactosidase protein can then be detected in frozen tissue sections using a chromogenic substrate. Therefore, pKZ1 mice can be used to detect SICR inversion events in vivo in different tissues. We have tested the pKZ1 mouse for its potential as a general mutagenesis model for detecting SICR in spleen in response to carcinogens which have widely different mechanisms of genotoxicity. Animals were given a single exposure of carcinogen and spleen cells were examined 3 days later for inversion events by histochemical staining of tissue sections. Mitomycin C, X-irradiation, etoposide and methylene chloride caused significant induction of inversion events in spleen tissue, ranging from 1.6- to 4.2-fold induction with the doses used here. This is the first time that inversion events induced by these carcinogens have been specifically studied in vivo in a mouse model and the findings expand the repertoire of mutation events known to be caused by these agents. We suggest that the pKZ1 mouse can be used as a general mutagenesis model for detection of SICR events and is likely to be a useful model for studying the mechanism of SICR in response to DNA damaging agents.
authors.affiliation: Department of Haematology and Genetic Pathology, Flinders University of South Australia and Flinders Medical Centre, Bedford Park, SA 5042, Australia. pam.sykes@flinders.edu.au
authors.forename: P J
authors.initials: PJ
authors.lastname: Sykes
authors.forename: A M
authors.initials: AM
authors.lastname: Hooker
authors.forename: A A
authors.initials: AA
authors.lastname: Morley
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D007446:Chromosome Inversion; D002875:Chromosomes / Q000187:drug effects* / Q000528:radiation effects; D004926:Escherichia coli / Q000235:genetics; D005047:Etoposide / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D007763:Lac Operon / Q000235:genetics; D008752:Methylene Chloride / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D016685:Mitomycin / Q000633:toxicity; D016296:Mutagenesis; D011995:Recombination, Genetic; D013154:Spleen / Q000187:drug effects / Q000528:radiation effects
chemical_list: D002273:Carcinogens; D016685:Mitomycin; D008752:Methylene Chloride; D005047:Etoposide