Genomic instability in chronic renal failure patients.

Patients suffering chronic renal failure (CRF) exhibit a high incidence of cancer, as well as high levels of genetic damage. We hypothesized that these patients show genomic instability as measured by increased radiosensitivity to the induction of genetic damage. The background levels of genetic damage and the net genetic damage after in vitro irradiation with 0.5 Gy were analyzed using the micronucleus assay in peripheral blood lymphocytes of 174 CRF patients and 53 controls. The net radiation-induced genetic damage was significantly higher in CRF patients with respect to controls. Among CRF patients, the levels of genetic damage were higher in those with prior incidence of cancer than in those without cancer; in addition, those CRF patients undergoing hemodialysis presented with higher levels of genetic damage than those in the advanced Stages (4-5) of the pathology. A positive association was observed between basal and net micronucleus frequency among CFR patients. However, no association was found between net genetic damage and parameters linked to the different stages of the pathology, such as urine creatinine levels and glomerular filtration rate. Our results indicate that CRF patients show increased radiosensitivity and that the degree of radiosensitivity is associated with the progression of the pathological stage of the disease.

Genotoxic evaluation of two halonitromethane disinfection by-products in the Drosophila wing-spot test.

Few studies on the genotoxicity of halonitromethanes (HNMs) have been done. This limited information on their potential genotoxic risk gives special relevance to the collection of new data on their potential genotoxic activity. In the present study we have analyzed the genotoxicity of two HNMs namely bromonitromethane (BNM) and trichloronitromethane (TCNM) in the in vivo wing somatic mutation and recombination test in Drosophila, also known as the wing-spot assay. This test is based on the principle that loss of heterozygosis and the corresponding expression of the suitable recessive markers, multiple wing hairs (mwh) and flare-3 (flr(3)), can lead to the formation of mutant clones in larval cells, which are then expressed as spots on the wings of adult flies. BNM and TCNM were supplied to third instar larvae (72+/-4 h-old) at concentrations ranging from 0.1 to 2 mM. The results showed that none of the three categories of mutant spots recorded (small, large, and twin) increased significantly by the treatments, independently of the dose supplied, indicating that the selected HNMs exhibit a lack of genotoxic activity in the wing-spot assay of Drosophila melanogaster. These results contribute to increase the genotoxicity database on the HNMs.