Loss of p53 in benzene-induced thymic lymphomas in p53+/- mice: evidence of chromosomal recombination.
The purpose of this study was to examine the role of chromosomal recombination in mediating p53 loss in benzene-induced thymic lymphomas in C57BL/6-Trp53 haploinsufficient (N5) mice (p53+/- mice). We characterized loss of heterozygosity (LOH) on chromosome 11 using seven microsatellite markers in 27 benzene-induced and 6 spontaneous thymic lymphomas. Eleven patterns of LOH were found between the induced and spontaneous tumors, with only one pattern being in common between the tumor groups. Nearly 90% (24 of 27) of benzene-induced tumors exhibited loss of the functional p53 allele locus, and 83% (20 of 24) of these tumors retained two copies of the disrupted p53 allele. The results indicate that benzene induces a high frequency of LOH on chromosome 11 in p53+/- mice, likely mediated by aberrant chromosomal recombination.
Boley
S E
SE
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
Anderson
E E
EE
French
J E
JE
Donehower
L A
LA
Walker
D B
DB
Recio
L
L
D000483:Alleles; D000818:Animals; D001554:Benzene; D015139:Blotting, Southern; D002875:Chromosomes; D017353:Gene Deletion; D018628:Gene Dosage; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000139:chemically induced* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D018895:Microsatellite Repeats; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013953:Thymus Neoplasms / Q000139:chemically induced* / Q000235:genetics*
D001554:Benzene