International study of factors affecting human chromosome translocations

Abstract

Abstract*Correspondence, page proofs, and reprint requests to: James D. Tucker, Ph.D., Department of Biological Sciences, 1370 Biological Sciences Building, 5047 Gullen Mall, Wayne State University, Detroit, TEL: (313) 577-2783, FAX: (313) 577-3602, EMAIL: E-mail: jtucker@biology.biosci.wayne.edu. z Retired Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from sixteen laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages vs. a linear relationship (p <0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes. NIH Public Access

Biological Dosimetry of Ionizing Radiation

“…Furthermore, translocations persist for many years in circulating lymphocytes and their frequency increases significantly with age and the lifetime conditions (alcohol, tobacco, pesticide exposure…) , (Sigurdson, 2008), (Grégoire, 2010). This increase has to be taken into consideration in evaluation of exposure and corrected for as a function of the age of the individual.…”

“…This increase has to be taken into consideration in evaluation of exposure and corrected for as a function of the age of the individual. The relationship between translocation yield and age is based on a linear-exponential model (Sigurdson, Ha, 2008):…”

Cytogenetic Biological Dosimetry Past, Present and Future Perspectives

“…Among these assays the control level (unexposed samples) of chromosomal alterations is in order of: micronuclei (3-35) > translocations (0-15) > dicentrics (1-4) > PCC (0-2) per 1000 cells analyzed [6]. For both MN and translocation assays influence of age on increasing level of chromosomal alterations was evident [6,20,21]. Moreover, smoking status suggests an acceleration of translocation ≥ age of 60 years old [21].…”

“…For both MN and translocation assays influence of age on increasing level of chromosomal alterations was evident [6,20,21]. Moreover, smoking status suggests an acceleration of translocation ≥ age of 60 years old [21]. Consequently, in cases of immediate and retrospective dose assessment using FISHbased translocation assay, the background frequency (age of exposed individuals) should always be considered.…”

“…The calculation of the biological radiation doses on the frequency of reciprocal translocations using 3-4 chromosomes (representing approximately 20% of the genome) showed that FISH technique can be used for retrospective group dosimetry for the doses above 25 cGy (one should score 1000 cells, genome equivalent) and for the individual dosimetry 2000 cells genome equivalent is recommended. For situation of exposure in dose range ~ 30 -200 cGy, 1000, and 500 cells genome equivalent, respectively should be sufficient, taking into account the factor of aging [18,20,21]. In order to reduce number of cells for analysis and to detect all structural as well as numerical aberrations simultaneously in one preparations a multi-colour FISH technique is developed and applied for whole genome analysis of human chromosomes using 23/24 different colours for 23/24 different human chromosomes [26].…”