Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case–control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case–control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors.

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

A dose estimation by chromosome analysis was performed on the 3 severely exposed patients in the Tokai-mura criticality accident. Drastically reduced lymphocyte counts suggested that the whole-body dose of radiation which they had been exposed to was unprecedentedly high. Because the number of lymphocytes in the white blood cells in two patients was very low, we could not culture and harvest cells by the conventional method. To collect the number of lymphocytes necessary for chromosome preparation, we processed blood samples by a modified method, called the high-yield chromosome preparation method. With this technique, we could culture and harvest cells, and then make air-dried chromosome slides. We applied a new dose-estimation method involving an artificially induced prematurely condensed ring chromosome, the PCC-ring method, to estimate an unusually high dose with a short time. The estimated doses by the PCC-ring method were in fairly good accordance with those by the conventional dicentric and ring chromosome (Dic+R) method. The biologically estimated dose was comparable with that estimated by a physical method. As far as we know, the estimated dose of the most severely exposed patient in the present study is the highest recorded among that chromosome analyses have been able to estimate in humans.

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We isolated and sequenced the rearranged genomic variable (V) and joining (J) gene segments of T cell receptor alpha-chain gene from two independent keyhole limpet hemocyanin (KLH)-specific suppressor T cell (Ts) hybridomas (BW5147 x C57BL/6 KLH-Ts). These nucleotide sequences were compared with those of germline DNA from kidney and also with cDNA of alpha-chain (VJ alpha 281) previously isolated from Ts hybridoma (34S-281) with KLH/H-2b Ts activity. The entire V alpha and J alpha sequences of all three Ts hybridomas were exactly identical and were encoded by the germline V alpha and J alpha gene segments without any mutations, except for 2-nucleotide deletions from both the 3' end of V alpha and 5' end of J alpha gene segments, respectively, and a 1-nucleotide (guanine) insertion in the junctional (N) region which was not encoded by the germline gene. Six additional KLH-Ts hybridomas, further analyzed, also possessed the same alpha-chain, indicating the preferential usage of the particular alpha-chain in these hybridomas. As chromosome analysis demonstrated a different pattern in each clone, these hybridomas appear to be independent. More surprisingly, 0.5-1.5% of the total functional T cell alpha-chain mRNA in the thymus and spleen of unprimed C57BL/6 mice was found to be of this particular alpha-chain. These results suggest that the repertoire of KLH-Ts is strictly limited.