Latent expression of p53 mutations and radiation-induced mammary cancer.
EF42 is a clonally derived preneoplastic cell lineage from irradiated mouse mammary tissue, which becomes neoplastic with time in vitro or in vivo. We now report that multiple mutations in p53 occur before the acquisition of the neoplastic phenotype. The selective expansion of mutant cells is accompanied by loss of heterozygosity at the p53 locus and c-myc amplification. Although p53 mutations represent critical early events, our data argue these mutations were not directly induced by radiation but arose in the progeny of irradiated cells several cell generations later. The data are consistent with a multistep model of carcinogenesis that identifies genomic instability as the earliest step.
Selvanayagam
C S
CS
Department of Radiation Therapy, University of Texas Medical Branch, Galveston 77555-0656, USA.
Davis
C M
CM
Cornforth
M N
MN
Ullrich
R L
RL
D000818:Animals; D001483:Base Sequence; D005260:Female; D016158:Genes, p53 / Q000235:genetics / Q000528:radiation effects*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009857:Oncogenes / Q000528:radiation effects; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length