Arsenic (As) is a known human carcinogen; however, very little is known about the health consequences of occupational exposure to As. In the present study, we assessed the genotoxic damage in the blood cells and in the buccal cells of south Indian glass factory workers who are occupationally exposed to As. The As content in the whole blood of 200 workers and 165 controls was evaluated with inductively coupled plasma mass spectrometry. Blood leukocytes from the subjects were monitored for the level of DNA damage using the Comet assay (mean comet tail length); buccal cells were used to determine the frequency of micronuclei (MN). The mean As concentration was significantly higher in the workers (56.76 microg/L) than in the controls (11.74 microg/L) (P < 0.001). The workers also had increased frequencies of MN in the buccal cells and increased levels of DNA damage in leukocytes compared to the controls (P < 0.001). There were significant correlations between the genotoxicity endpoints that were evaluated and blood As concentration, smoking, age, and the duration of working in the factory. Also, a significant correlation was observed between the frequency of MN and comet tail-length for the worker samples. Our findings indicate that chronic occupational exposure to As is genotoxic and that the Comet assay and micronucleus test are useful assays for evaluating genotoxicity in humans occupationally exposed to As.

Abstract:Wilson disease is an autosomal recessive disorder characterized by toxic accumulation of copper in a number of organs such as liver and brain, which results in significant disability or death if left untreated. Wilson disease is caused by mutations in ATP7B, a copper transporter. We analyzed 108 American Wilson disease patients, who are predominantly White, for mutations in ATP7B. Consistent with studies from other populations, H1069Q was the most common mutation in this group of patients, accounting for 40.3% of the sequenced alleles; 26 of the 108 patients were homozygous, and 35 patients were heterozygous for this mutation. We also identified 24 additional ATP7B mutations, of which five were novel. The five new mutations consist of two insertion mutations (2302insT and 3843insT), one splice site mutation (IVS11+2:T>A), one combination of deletion (2bp) and insertion (19bp) (3693-3697delins19bp), and one missense mutation (G1213S). All variants are predicted to be disease-causing mutations. Ninety six percent of all mutations we identified were clustered in regions encoding the C-terminal half (catalytic domain) of the ATP7B protein. Furthermore, we found that 84% of the mutant alleles identified in the American population are located in exons 14 and 18.