A computational approach to the relationship between radiation induced double strand breaks and translocations.
A theoretical framework is presented which provides a quantitative analysis of radiation induced translocations between the ab1 oncogene on CH9q34 and a breakpoint cluster region, bcr, on CH 22q11. Such translocations are associated frequently with chronic myelogenous leukemia. The theory is based on the assumption that incorrect or unfaithful rejoining of initial double strand breaks produced concurrently within the 200 kbp intron region upstream of the second abl exon, and the 16.5 kbp region between bcr exon 2 and exon 6 interact with each other, resulting in a fusion gene. for an x-ray dose of 100 Gy, there is good agreement between the theoretical estimate and the one available experimental result. The theory has been extended to provide dose response curves for these types of translocations. These curves are quadratic at low doses and become linear at high doses.
Holley
W R
WR
Division of Life Sciences, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.
Chatterjee
A
A
D000818:Animals; D002461:Cell Line, Transformed; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005091:Exons; D016313:Genes, abl; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008957:Models, Genetic; D008962:Models, Theoretical; D005810:Multigene Family; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011336:Probability; D014178:Translocation, Genetic / Q000528:radiation effects*