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The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM., (© 2014 Wiley Periodicals, Inc.)

We evaluated the influence of several DNA repair gene polymorphisms on the frequency of chromosomal aberrations (CAs) analyzed in peripheral lymphocytes, using the fluorescence in situ hybridization technique. The CA data were obtained from an earlier study of 84 healthy nonsmokers (48 women and 36 men) carefully characterized for indoor radon exposure. The frequency of translocations showed a wide interindividual variability, which was only partly explained by age. To investigate the potential role of DNA repair polymorphisms in this variation, genotypes of DNA repair genes OGG1 (codon 326), XPD (codon 751), XRCC1 (X-ray repair cross-complementing group 1) (codons 194, 280, and 399), and XRCC3 (X-ray repair cross-complementing group 3) (codon 241) were determined from leukocyte DNA using polymerase chain reaction-based methods. Negative binomial regression models were applied to evaluate the effect of the polymorphisms and other factors (age, gender, radon exposure, and medical exposure) on the frequency of CAs. No interactions between genotypes and radon, medical exposure, or gender were found. Carriers of the XRCC1 codon 280His variant allele had a two-fold increase (frequency ratio [FR] = 2.01, 95% confidence interval [CI] = 1.01-3.98; P = 0.046) in unstable exchanges (dicentrics and ring chromosomes). In addition, the XRCC3 codon 241 homozygous variant genotype (Met/Met) was associated with an increase (FR = 1.70, 95% CI = 1.06-2.74; P = 0.028) in two-way translocations when age was taken into account in the analysis. Our data suggest that the XRCC1 280His and XRCC3 241Met alleles affect individual CA levels, most probably via influencing the DNA repair phenotype.

Very high concentrations of naturally occurring radionuclides are encountered in Finnish groundwaters and wells. Radon ingested through drinking water can cause considerable radiation to the stomach. We assessed the effect of natural uranium and other radionuclides in drinking water on the risk of stomach cancer. Subjects (n = 144,627) in the base cohort had lived outside the municipal tap water system during 1967-1980. A subcohort of 4,590 subjects was formed for use as a reference group by random sampling of the base cohort, with stratification by age and sex. Within the subcohort, 371 subjects had used drinking water from drilled wells prior to 1981. Stomach cancer cases within the subcohort were identified through a cancer registry, and cases using water from drilled wells were selected. Activity concentrations of radon, radium-226 and natural uranium in the drinking water were analyzed using radiochemical and alpha spectrometric methods. The median activity concentration of radon in well water was 130 Bq/l for both the 88 stomach cancer cases and the 274 subjects in the subcohort. Median radium concentrations were 0.007 Bq/l for cases and 0.010 Bq/l for the subcohort, with a median uranium concentration of 0.07 Bq/l for both groups. Risk of stomach cancer was not associated with exposure to radon or other radionuclides. The hazard ratio of stomach cancer was 0.68 for radon (95% CI 0.29-1.59 at 100 Bq/l water), 0.69 per Bq/1 for radium-226 (95% CI 0.33-1.47) and 0.76 per Bq/1 for uranium (95% CI 0.48-1.21). Our results do not indicate an increased risk of stomach cancer from ingestion of radon or other natural radionuclides through drinking water at these exposure levels.

We describe a 2(1/2)-year-old boy with a ring chromosome 13 with distal deletion of 13q32-->qter and celiac disease., (Copyright 2000 Wiley-Liss, Inc.)