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Studies focusing on possible genotoxic effects of excess fluoride are contradictory and inconclusive. Currently, studies have reported a probable link to oxidative stress, DNA damage and apoptosis induced by fluoride in rat hepatocytes. We developed an in vivo study administering three doses of fluoride by gavage given to rats for 60 day. Micronucleus test was applied to investigate genotoxic potential of fluoride. The TUNEL method determined DNA fragmentation and apoptosis. Biochemical parameters to investigate mitochondrial swelling and oxidative stress. Semi-quantitative RT-PCR and immunostaining to determine mRNA and protein expression of antioxidant enzymes. Analyses of the hepatic function and morphology were performed. Our results revealed the genotoxic potential of fluoride but did not confirm mitochondrial swelling nor an increase of positive TUNEL labelling induced by fluoride, indicating absence of apoptosis. Oxidative stress induction was confirmed and is probably associated to DNA damage. Cell death events such as empty nuclear spaces, cytoplasm degeneration, nuclear pyknosis, karyorrhexis and karyorrhexis followed by karyolysis were observed. Hepatic function did not appear to be significantly modified makes no evidence of necrosis and suggesting other cell death pathway, the autophagic. In conclusion, prolonged fluoride intake at chosen concentrations caused imbalance of the cellular oxidative state, affected DNA and disrupted cellular homeostasis. It is recommended that fluoride supplementation requires a fresh consideration in light of the current study.

Introduction:Hodgkin's lymphoma (HL) is a lymphoid malignancy with a worldwide incidence is 2-4/100,000 individuals/year. HL represents 5% of all childhood cancers and is 30-40% of all malignant lymphomas. Treatment for HL involves a combination of radiation and chemotherapy. One of the most common treatment schemes uses ABVD (adriamycin, bleomycin, vinblastine, dacarbazine), a cocktail of genotoxic agents. Although survival rate for HL is up to 95%, cancer therapy could produce persistent genetic damage in the survivors.Objective: The goal of this study is to determine the time course of chromosomal damage in lymphocytes of patients with HL before, during and after ABVD/radiotherapy. Material and methods: Five patients diagnosed with HL provided peripheral blood samples before, during and one year after ABVD chemotherapy. In addition, 5 healthy individuals provided a single blood sample. All participants in the study signed informed consent. Chromosomal aberrations were evaluated by M-FISH (SpectraVysion) in 50-100 karyotypes per sample. Spectral karyotyping for each cell was analysed with Isis software. Statistical comparisons were done with the Kruskal-Wallis and Mann-Whitney U tests and a p < 0.05 was considered significant.Results: Average frequencies of structural chromosomal aberrations (CA) in samples from patients with HL were 6.3, 7.1 and 23.0% before treatment, during, and one year after treatment, respectively. CA frequency in healthy individuals was 2.4%. A significant difference (p < 0.002) was observed when comparing groups. Chromosomal damage was observed in all samples, and rejoined structural chromosomal aberrations (RCA), such as translocations and dicentrics, were the most common type. No clonal aberrations were observed.Conclusions: Our study showed that ABVD cause genotoxic damage in peripheral blood lymphocytes of HL patients. Interestingly, the highest frequency of RCA/cell was observed in samples analyzed one year after treatment and this was significantly different from what was found before treatment (23% vs 6%). Both rejoined and non-rejoined aberrations are observed one year after treatment indicating that new aberrations are continuously produced and that there may be alterations affecting genes involved in DNA repair. These results suggest that ABVD/radiotherapy causes sublethal damage in hematopoietic stem cells and can lead to persistent genomic instability.Financial support: 099-CONACYT-Salud.http://dx.

analyzed by ANOVA followed by Tukey's post hoc test, adopting p < 0.05 as a limit of significance. Results: We found a significant decrease in AOPP levels in 192RR subjects (0.64 nmol/ml, p < 0.01) compared to WT (1.76 nmol/ml) and 192QR (1.60 nmol/ml) workers; serum AGE were lower in 192RR workers (147,221 AU/ml, p < 0.05) than in WT (161,400 AU/ml) and 192QR (152312 AU/ml) subjects. The analysis of the allele frequencies distribution demonstrated that 192Q (WT) wild-type allele was significantly more frequent than 192R mutated allele (0.74 vs 0.26) in the sample. WT allele was mainly represented by homozygote genotype 192QQ (51%), the mutated one by heterozygote 192QR (45.4%). Conclusions: These results are comparable with those reported in an our previous study conducted in a smaller sample of farmers employed in a farm located in Sicily; they also confirm that chronic OP pesticide exposure may result in long-lasting oxidative stress.

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