ABSTRACT
The aims of the present study were to assess clastogenic and aneugenic properties of welding fumes using fluorescent in situ hybridization (FISH) with a human pancentromeric DNA probe. The involvement of genetic polymorphisms in DNA repair genes (p.Arg399Gln of XRCC1 and p.Thr241Met of XRCC3) and in detoxification genes (GSTM1 and GSTT1) on the centromere content of micronuclei (MN) was also evaluated. This study included 27 male welders working without any collective protection device and a control group (n = 30). The welders showed significantly higher levels of chromosome/genome damage compared to the controls. The frequencies of MN and centromere-positive MN (C+MN) per 1,000 binucleated cells were significantly higher in the exposed group than in the control group (7.1 per thousand +/- 3.7 versus 4.9 per thousand +/- 1.8; P = 0.012 and 3.5 per thousand +/- 1.8 versus 2.4 per thousand +/- 1.2; P = 0.018, respectively, Mann-Whitney U-test). The centromere-negative MN (C-MN) frequency was higher in the exposed subjects than in the controls (3.6 per thousand +/- 3.4 versus 2.5 per thousand +/- 1.4), but the Mann-Whitney U-test did not yield a significant result. In the total population, the GSTM1 and GSTT1 polymorphisms significantly affected the frequencies of C-MN and C+MN defined by FISH. GSTM1 positive subjects showed an increased C-MN frequency and GSTT1 null subjects showed an elevated C+MN frequency. When GSTM1 and GSTT1 genotypes were included in multiple regression analysis, the effect of the occupational exposure could better be demonstrated; both C+MN and C-MN were significantly increased in the welders. Our results suggest that the combined analysis of genetic polymorphisms and centromeres in MN may improve the sensitivity of the micronucleus assay in detecting genotoxic effects.
Subject(s)
Centromere/ultrastructure , DNA-Binding Proteins/genetics , Glutathione Transferase/genetics , Micronucleus Tests/methods , Occupational Exposure , Polymorphism, Genetic , Adult , Humans , In Situ Hybridization, Fluorescence , Male , Mutagens , Smoking , Welding , X-ray Repair Cross Complementing Protein 1ABSTRACT
Ultraviolet A radiation (UVA; 320-400 nm) constitutes more than 90% of the terrestrial UV solar energy. This type of radiation generates reactive oxygen species and consequently induces DNA damage. UVA irradiation is now considered to be an important carcinogen agent especially in the development of melanoma. UVA radiation is known to activate several pathways in mammalian cells. We have used cDNA arrays to analyze differential gene expression in primary cultures of human melanocytes in response to 365-nm UVA. Among 588 genes studied, 11 were overexpressed. These genes included genes involved in cell cycle regulation (GADD45, CIP1/WAF1), in stress response (HSP70, HSP40, HSP86), in apoptosis (GADD153, tristetraproline) and genes encoding transcription factors (EGR-1, ETR-101, c-JUN, ATF4). This coordinate gene regulation was confirmed by real-time quantitative RT-PCR.
Subject(s)
Genes , Melanocytes/radiation effects , Ultraviolet Rays , Cell Differentiation , Cell Division , DNA Repair , Gene Expression Regulation/radiation effects , Humans , Melanocytes/metabolism , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
The APOE4 allele is widely accepted as a major risk factor for late-onset Alzheimer's disease (AD). Recently, it has been reported that polymorphisms in the APOE promoter and in the alpha2-macroglobulin gene (A2M) are associated with AD. We have analyzed the distribution of APOE alleles, -219T/G APOE promoter polymorphism, and A2M/A2Mdel polymorphism in a large case-control study. Our results showed that APOE genotype was the only informative marker of AD risk contrary to -219T/G and A2M/A2Mdel polymorphism. In AD patients however, a strong linkage disequilibrium was observed between the T allele of -219T/G polymorphism and APOE4 allele. This result indicates that -219T/G APOE promoter polymorphism is a risk factor for AD by increasing the APOE4-associated risk.
Subject(s)
Alzheimer Disease/genetics , Apolipoproteins E/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , alpha-Macroglobulins/genetics , Aged , Alleles , Apolipoprotein E4 , France , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Linkage Disequilibrium , Reference Values , Risk Factors , White PeopleABSTRACT
This study presents a pedagogical work carried out with a group of 13 school nurses of the Academy of Rennes, as part of a course in survey methodology. A descriptive survey aiming to achieve a better understanding of experienced health status of nurses, and of its repercussions on the execution of their missions, was implemented during the course, as a result of the demand and the expertise of the participants. Overall, nurses report to be in good health. However, one can not underestimate the existence of a group at risk (5% of the sample) that often suffers somatic troubles accompanied by sleep disorders and anxiety, as these risks concern primarily permanent staff nurses working in boarding establishments, with half of them falling into this category. A demand for regular monitoring of their health was clearly expressed through the study. This may be the object of a subsequent study by an academic team.