Reconstruction of doses from ionizing radiation using fluorescence<i>in situ</i>hybridization techniques

Edwards, Alan; Szłuińska, M.; Lloyd, David

doi:10.1259/bjr/24766640

Cited by 24 publications

(27 citation statements)

References 21 publications

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“…Chromosome changes also play a major role in carcinogenesis (2) and there is increasing evidence that their presence in peripheral blood lymphocytes provides a marker of cancer risk (3). For the assessment of historical and chronic exposures to ionizing radiation the translocation is the aberration of choice (1,(4)(5)(6). Translocations are stable aberrations that persist through cell division and their presence in peripheral blood lymphocytes is maintained because descendants of irradiated bone marrow stem cells carrying translocations survive and appear in the circulating blood.…”

Section: Introductionmentioning

confidence: 99%

Retrospective Biodosimetry among United States Radiologic Technologists

Bhatti

Preston²,

Doody

et al. 2007

Radiation Research

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Section: Introductionmentioning

confidence: 99%

Retrospective Biodosimetry among United States Radiologic Technologists

Bhatti

Preston²,

Doody

et al. 2007

Radiation Research

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“…SEER cancer database data 49 on age dependence of background CML incidence; and, for comparison, data on age dependence of background chromosome translocations developed to assist radiation biodosimetry (reviewed in Edwards et al 50 and Sigurdson et al 51 ).…”

Section: Data Consideredmentioning

confidence: 99%

“…Quantitative models that analyze CML treatment have not yet incorporated analyses of CML incidence with age. This section discusses results, relevant to any such unification, on how background in vivo chromosome translocation levels increase with age.The translocation data presented in Figure 5 were generated as controls for radiation biodosimetry (reviewed in Edwards et al, 50 Sigurdson et al, 51 and Tucker 52 ) and do not single out BCR-ABL. In these data, accumulated numbers of clones with translocations are counted at various ages; a clone with a specific translocation is counted only once no matter how many cells the clone has.…”

mentioning

confidence: 99%

“…For the age-induced case, relevant data on translocations is fairly firm 51 (see Figure 5B), and CML data are very firm. 49 In the radiation-induced case, firm results on translocations are available both theoretically and experimentally [50][51][52]78 ; the relevant data on CML 48 has been discussed in connection with Figure 5.In addition to these results, one needs only the conditional probability P(BA|trans) that a cell acquires a BCR-ABL translocation given that it acquires a translocation. P(BA|trans) can be estimated to be twice the product of the relevant BCR and ABL intron sizes divided by the genome size squared.…”

mentioning

confidence: 99%

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Quantitative modeling of chronic myeloid leukemia: insights from radiobiology

Radivoyevitch

Hlatky

Landaw

et al. 2012

Blood

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Mathematical models of chronic myeloid leukemia (CML) cell population dynamics are being developed to improve CML understanding and treatment. We review such models in light of relevant findings from radiobiology, emphasizing 3 points. First, the CML models almost all assert that the latency time, from CML initiation to diagnosis, is at most ϳ 10 years. Meanwhile, current radiobiologic estimates, based on Japanese atomic bomb survivor data, indicate a substantially higher maximum, suggesting longer-term relapses and extra resistance mutations. Second, different CML models assume different numbers, between 400 and 10 6 , of normal HSCs. Radiobiologic estimates favor values > 10 6 for the number of normal cells (often assumed to be the HSCs) that are at risk for a CML-initiating BCR-ABL translocation. Moreover, there is some evidence for an HSC dead-band hypothesis, consistent with HSC numbers being very different across different healthy adults. Third, radiobiologists have found that sporadic (background, agedriven) chromosome translocation incidence increases with age during adulthood. BCR-ABL translocation incidence increasing with age would provide a hitherto underanalyzed contribution to observed background adult-onset CML incidence acceleration with age, and would cast some doubt on stage-number inferences from multistage carcinogenesis models in general. (Blood. 2012; 119(19):4363-4371) IntroductionChronic myeloid leukemia (CML) is characterized by Ph ϩ cells, that is, cells having a Philadelphia (BCR-ABL) chromosome translocation. 1,2 Treatment with the tyrosine kinase inhibitor (TKI) imatinib mesylate ("imatinib"), which suppresses bcr-abl oncoprotein action, 3 improves patient prognosis dramatically. 4 However, in some cases this treatment fails, a problem mitigated but not fully solved by the use of more recently developed TKI. 5,6 Moreover, many patients may need to continue TKI treatment indefinitely to avoid relapse. 7 CML is one of the best understood cancers; it has a simpler etiology than most cancers 8 and its time course is comparatively easy to monitor in the clinic. 9,10 Consequently, despite being much less prevalent than major solid tumors, CML has often been regarded as a kind of "model organism" for quantitative modeling of human carcinogenesis. 11,12 CML cell population dynamicsIn this review, we emphasize how radiobiologic studies impact CML models grounded in understanding underlying cell population dynamics. These models track CML time evolution by differential equations and/or stochastic formalisms. Such biologically based quantitative models are more ambitious, more comprehensive, and as yet less definitive than models often used in statistical analyses, which emphasize correlations analyzed by adjusting parameters in functions chosen mainly for mathematical convenience.After work by Rubinow and Lebowitz 13 on hematopoiesis, biologically based, mathematical CML models were pioneered by Clarkson and coworkers. 14 Many additional models have been suggested in the last decade. Recent a...

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“…Thus for protracted low-LET exposure, translocation frequencies should increase with cumulative dose and provide a good measure of total dose. Indeed it has been suggested that the main application for FISH translocation analysis is in assessing long-term low-dose-rate cumulative exposure and thus, it is a useful tool in dose reconstruction for epidemiological studies (5).…”

Section: Introductionmentioning

confidence: 99%