Li-Fraumeni and Li-Fraumeni-like syndrome among children diagnosed with pediatric cancer in Southern Brazil.

BACKGROUND: Pediatric cancers are a feature in patients with Li-Fraumeni syndrome and its variant Li-Fraumeni-like syndrome (LFS/LFL). To the best of the authors' knowledge, TP53 germline mutations are currently the only molecular defect known to be associated with this disease. Recently, a specific germline mutation in this gene, p.R337H, has been reported at a high prevalence in Brazil. METHODS: The prevalence of LFS/LFL was investigated in children with cancer who were diagnosed with tumors on the LFS/LFL spectrum and in a small consecutive series of controls without cancer. The prevalence of the germline p.R337H mutation and of other germline TP53 mutations was investigated in a general group of children with cancer and exclusively in children fulfilling the clinical criteria for LFS/LFL, respectively. RESULTS: Among the 65 children without cancer, 1.5% had a family history of LFL whereas of the 292 children with cancer, 25.3% had a family history of LFL (P < .001). Screening for the p.R337H mutation identified 11 carriers (3.7%), 9 of whom were diagnosed with adrenocortical carcinomas (ACC) and 2 of whom were diagnosed with choroid plexus carcinomas. One of the ACC probands was homozygous mutant. The Brazilian founder haplotype and loss of heterozygosity at the p.R337H locus were present in all carriers. In addition, direct sequencing of the entire TP53 coding region and gene rearrangement analysis of probands fulfilling the criteria for LFL (Eeles 2 criteria, Birch and/or Chompret criteria) and who were negative for the p.R337H mutation revealed a DNA-binding domain pathogenic mutation, p.G245S, in 1 child. CONCLUSIONS: TP53 p.R337H testing should be offered to Brazilian children diagnosed with ACC and choroid plexus carcinoma. A significant percentage of children with cancer in southern Brazil fulfill the criteria for LFL and should be referred for genetic risk assessment.

Increased micronucleated cell frequency related to exposure to radiation emitted by computer cathode ray tube video display monitors

It is well recognized that electromagnetic fields can affect the biological functions of living organisms at both cellular and molecular level. The potential damaging effects of electromagnetic fields and very low frequency and extremely low frequency radiation emitted by computer cathode ray tube video display monitors (VDMs) has become a concern within the scientific community. We studied the effects of occupational exposure to VDMs in 10 males and 10 females occupationally exposed to VDMs and 20 unexposed control subjects matched for age and sex. Genetic damage was assessed by examining the frequency of micronuclei in exfoliated buccal cells and the frequency of other nuclear abnormalities such as binucleated and broken egg cells. Although there were no differences regarding binucleated cells between exposed and control individuals our analysis revealed a significantly higher frequency of micronuclei (p < 0.001) and broken egg cells (p < 0.05) in individuals exposed to VDMs as compared to unexposed. We also found that the differences between individuals exposed to VDMs were significantly related to the sex of the individuals and that there was an increase in skin, central nervous system and ocular disease in the exposed individuals. These preliminary results indicate that microcomputer workers exposed to VDMs are at risk of significant cytogenetic damage and should periodically undergo biological monitoring.

Protective immune response against methicillin resistant Staphylococcus aureus in a murine model using a DNA vaccine approach.

Methicillin resistant Staphylococcus aureus (MRSA) are a major pathogen responsible for serious hospital infections worldwide. These bacteria are resistant to all beta-lactam antibiotics due to the production of an additional penicillin binding protein, the PBP2a, encoded by the mecA gene, which shows low affinity for this class of antibiotics. In this study, we cloned an internal region from the transpeptidase domain from the PBP2a into a mammalian expression vector, to be used as DNA vaccine in a Murine model. After three sets of DNA vaccination, the immune response represented by antibodies against a fragment of PBP2a was evaluated by enzyme linked immunosorbent assay (ELISA), showing a significant antibody response. The antibacterial effect of the DNA vaccine was evaluated by intraperitoneal immunization and challenge with a sublethal dose of MRSA for 7 days in mice. After the challenge, the number of bacteria from kidneys from immunized and non-immunized mice were determined. Kidneys from immunized mice had 1000 times less on bacteria than the positive controls (non-immunized mice). The response specificity indicates no effects against the normal PBPs from staphylococci and no effects against Gram positive rods from normal intestinal flora. Our results indicate that the immunization against the PBP2a from MRSA using a DNA vaccine approach could be used as a new strategy to efficiently fight these multiresistant bacteria.

Avaliaçäo da genotoxicidade em cirurgiöes-dentistas da cidade de Pelotas-RS através do teste de micronúcleos em células esfoliadas da mucosa bucal / Genotoxicity evaluation in dentists of Pelotas city-RS through micronucleus test in bucal exfoliated mucosal cells

Milhöes de trabalhadores em vários setores ocupacionais correm o risco potencial de estarem expostos a substâncias perigosas. Há alguns anos tem sido debatido o amálgama dentário e seu efeito potencial par a saúde. O objetivo deste estudo foi avaliar o efeito do mercúrio do amálgama nos cirurgiöes-dentistas expostos a essa substância, por pelo menos cinco anos. Muitas substâncias säo genotóxicas e podem causar alteraçöes genéticas nas células somáticas de trabalhadores expostos. Neste estudo, foi utilizado o teste de micronúcleos (MN) em células esfoliadas, por ser um teste de baixo custo, näo invasivo, no qual a formaçäo de MN é um biomarcador para detectar efeitos endógenos do estilo de vida, exposiçöes ocupacionais e ambientais a genotóxicos, como também, a proteçäo de vários compostos em estudos de intervençäo. A freqüência de células com micronúcleos em cirurgiöes-dentistas com hábito alcoólico (4,43CMN ñ4,16) foi significativamente mais baixa (P <0,001) do que a dos dentistas sem hábito alcoólico (14,50CMNñ16,72). Os fumantes expostos apresentaram freqüência de células com micronúcleos (4,50CMN ñ2,12) significativamente mais baixa (P <0,001) do que a dos näo fumantes (10,62CMN ñ14,06). A idade e o tempo de trabalho näo influenciaram na freqüência de células com micronúcleos nestes profissionais