Tissue expresion of the genes mutyh and ogg1 in patients with sporadic colorectal cancer / Expressão tecidual dos genes mutyh e ogg1 em doentes com câncer colorretal esporádico

ABSTRACT Background: MTUYH and OGG1 genes have importance in the base excision repair systems of oxidized DNA bases. Modification of the tissue expression of these genes is related to the increased risk of developing colorectal cancer. Aim: To evaluate the tissue expression of MUTYH and OGG1 comparing normal and neoplastic tissues of patients with sporadic colorectal cancer and to correlate it with clinical and histopathological variables. Method: MUTYH and OGG1 tissue expression was quantified by RT-PCR in patients with colorectal cancer and the values were compared in normal and neoplastic tissues. MUTYH and OGG1 expression was measured and normalized to the constitutive 18S gene. The level of expression of both genes was correlated with the variables: age, gender, tumor location, size of the tumor, histological type, degree of cell differentiation, invasion depth in the intestinal wall, angiolymphatic infiltration, lymph node involvement and TNM staging. Results: Was found downregulation of both genes in neoplastic when compared to normal tissue. There was downregulation of the MUTYH in larger tumors and in patients with angiolymphatic invasion. Tumors with more advanced TNM stages (III and IV) presented downregulation of both genes when compared to those with earlier stages (I and II). Conclusion: The MUTYH and OGG1 genes present downregulation in the more advanced stages of colorectal cancer.

RESUMO Racional: Os genes MUTYH e OGG1 possuem importância nos sistemas de reparo por excisão de bases oxidadas do DNA. Modificação na expressão tecidual desses genes encontra-se relacionada ao maior risco do desenvolvimento do câncer colorretal. Objetivo: Avaliar a expressão tecidual dos genes MUTYH e OGG1 comparando tecidos normais e neoplásicos de portadores de câncer colorretal esporádico e correlacioná-la com variáveis clínicas e histopatológicas. Método: Avaliou-se por PCR, em tempo real, a expressão tecidual dos genes MUTYH e OGG1 em 49 portadores de câncer colorretal comparando tecidos normais e neoplásicos. A expressão dos genes MUTYH e OGG1 foi quantificada e normalizada com o gene constitutivo 18S. A intensidade de expressão de ambos os genes foi correlacionada as variáveis: idade, gênero, localização do tumor, tamanho do tumor, tipo histológico, grau de diferenciação celular, profundidade de invasão na parede intestinal, invasão angiolinfática, linfonodos comprometidos e estadiamento TNM. Resultados: Encontrou-se menor expressão de ambos os genes no tecido neoplásico quando comparado ao tecido normal. Houve menor expressão do gene MUTYH nos tumores com maiores dimensões e nos doentes que apresentavam invasão angiolinfática. Tumores com estadios mais avançados (III e IV) apresentavam expressão menor de ambos os genes quando comparados àqueles com estadios mais precoces (I e II). Conclusão: Os genes MUTYH e OGG1 apresentam menor expressão tecidual nos estadios mais avançados do câncer colorretal.

Influence of bleaching and desensitizing gel on bond strength of orthodontic brackets

OBJECTIVE: The objective of this study was to assess, in vitro, the influence of bleaching gel and the use of desensitizing agent over bond strength of ceramic brackets bonded to bovine enamel. METHODS: One hundred bovine incisors were selected and randomly divided into five groups (n = 20): Group 1, control group (without bleaching); Group 2, bleached with 35% hydrogen peroxide; Group 3, bleached with 35% hydrogen peroxide (three applications, 15 minutes each) and desensitizing agent applied for 10 minutes; Group 4, bleached with 35% hydrogen peroxide for 40 minutes; Group 5, bleached with 35% hydrogen peroxide for 40 minutes with desensitizing agent applied for 10 minutes. Brackets were bonded 7 days after bleaching and submitted to shear bond strength test after 24 hours at a compression rate of 1 mm/minute. After fracture, the adhesive remnant index (ARI) was assessed under stereoscopic at 40 x magnification. Shear strength data (MPa) were submitted to one-way ANOVA and Tukey's test with significance level set at 5%. RESULTS: Group 5 (29.33 MPa) showed significantly higher bond strength than Group 1 (19.19 MPa), Group 2 (20.59 MPa) and Group 4 (23.25 MPa), but with no difference in comparison to Group 3. There was no significant difference among the other groups. The adhesive remnant index showed predominance of score 3, that is, all resin remained adhered to enamel for all groups. CONCLUSION: Bleaching with 35% hydrogen peroxide with calcium associated with desensitizing agent application produced higher bond strength values of brackets bonded to bovine enamel. .

OBJETIVO: o objetivo do presente estudo foi avaliar, in vitro, a influência do gel clareador e da utilização de dessensibilizante na resistência adesiva de braquetes cerâmicos colados ao esmalte bovino. MÉTODOS: cem incisivos bovinos foram aleatoriamente divididos em cinco grupos (n = 20). Grupo 1, sem clareamento (controle); Grupo 2, clareamento com peróxido de hidrogênio a 35%; Grupo 3, clareamento com peróxido de hidrogênio a 35%, sendo três aplicações de 15 minutos cada, e aplicação do dessensibilizante por 10 minutos; Grupo 4, clareamento com peróxido de hidrogênio a 35% durante 40 minutos; Grupo 5, clareamento com peróxido de hidrogênio a 35% durante 40 minutos e aplicação do dessensibilizante durante 10 minutos. Os braquetes foram colados sete dias após o clareamento e submetidos ao teste de resistência ao cisalhamento após 24 horas, a uma velocidade de compressão de 1mm/minuto. Após a fratura, avaliava-se o braquete, com lupa estereoscópica, com magnificação de 40x, e o Índice de Remanescente Adesivo (IRA). Os dados de resistência ao cisalhamento (MPa) foram submetidos à análise de variância e ao teste de Tukey, com nível de significância de 5%. RESULTADOS: os resultados mostraram que as amostras do Grupo 5 apresentaram resistência de união significativamente superior à dos grupos 1, 2 e 4, mas sem diferença do Grupo 3. Não houve diferença significativa entre a resistência de união dos demais grupos. O Índice de Remanescente Adesivo mostrou predominância do escore 3, ou seja, toda resina permaneceu aderida ao esmalte, para todos os grupos. CONCLUSÃO: pôde-se concluir que o clareamento com peróxido de hidrogênio a 35%, com cálcio associado à aplicação do dessensibilizante, produziu maior resistência dos braquetes ao esmalte bovino. .

DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia

DNA repair is one of the central defense mechanisms against mutagenic exposures. Inherited SNPs of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. Saudi Arabia harbors enormous genetic and cultural diversity. In the present study we aimed to determine the genotype and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386 healthy individuals residing in the central region of Saudi Arabia and compare them with HapMap and other populations. The genotype and allele frequencies of the four DNA repair gene loci in central Saudi population showed a distinctive pattern. Furthermore, comparison of polymorphisms in these genes with other populations also showed a unique pattern for the central Saudi population. To the best of our knowledge, this is the first report that deals with these DNA repair gene polymorphisms among the central Saudi population.

Mutación homocigota en la línea germinal del gen MUTYH en una paciente chilena con poliposis adenomatosa familiar / Homozygous germline mutation in MUTYH gene in familial adenomatous polyposis

Recently, MUTYH mutations have been reported to predispose to the development of polyposis. However, polyposis caused by mutations in MUTYH has been characterized as an autosomal recessive hereditary disease, different from the autosomal dominant pattern observed in polyposis caused by APC mutations. We report a 41-year-old female consulting for anemia. Colonoscopy detected multiple sessile polyps and a cecal carcinoma. The patient was operated and in the surgical piece, the tumor invaded serosa and there was lymph node involvement. Approximately 100 polyps were found. The patient received 5-fluorouracil, as adjuvant therapy. The patient had a sister (of a total of 12 brothers) with a colorectal carcinoma. The genetic study identified a homozygous mutation of the MUTYH gene, called c.340T > C, that produces an amino acid change of tyrosine for histidine called p.Y114H. The sister with colorectal cancer was a heterozygous carrier of this mutation.

DNA damage and related modifier genes in Italian Cystic fibrosis patients

Cystic Fibrosis (CF) is an autosomal recessive multisystemic disorder showing a highly heterogeneous phenotype, even among siblings carrying identical CFTR mutations. Moreover, oxidative stress is of central importance in the pathogenesis of cystic fibrosis. The present study seeks to value the presence of oxidative damage in CF patients and the possible modifier effect of repair and glutathione-S-transferase genes. We analysed the presence of DNA damage in leukocytes of 63 CF patients at an Italian CF centre and 63 controls, through the alkaline Comet assay to detect DNA strand breaks. Furthermore, controls and 93 CF subjects were genotyped for 5 genes by RFLP-PCR (XRCC1,0GG1,GSTP1) and PCR assay (GSTM1, GSTT1). No difference in Comet assay values was observed comparing controls to CF patients, although CF subjects showed slightly higher mean values. The crude Odds-Ratio (OR) was higher than one for XRCC1 and GSTP1 genotypes and liver status and for XRCC1 and OGG1 genotypes and pancreatic insufficiency, but in all cases the p-values were not significant. In this case-control study, neither DNA damage ñor gene polymorphisms seem to influence CF manifestation.