<p>The aims of this study were to document the levels of cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) in serum and their relations to symptoms, clinical findings, and other factors in order to improve the possibilities of detecting early deficiency of vitamin B12 or folate, and to study the effects of cobalamin and folic acid treatment over a three-year period.</p><p>The study population consisted of a 20% random sample of persons 70 years or older living in Älvkarleby in mid-Sweden. They were invited to a survey and 224 (88.4%) persons responded. Data were obtained by questionnaire, laboratory investigations and physical examination for the period 1993 – 1999.</p><p>In a multivariate analysis performed at baseline, serum MMA and tHcy were significantly and independently correlated to age, serum cobalamin, and creatinine levels, and tHcy also to sex and serum folate. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin or mean red cell volume. Almost half of the study population had signs of low tissue levels of vitamin B12 or folate. Among those who took multivitamin preparations, the proportion was much lower, 25%.</p><p>Among traditional symptoms and clinical findings that have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis were significantly associated with abnormal serum folate and tHcy levels. Traditional symptoms of vitamin deficiency may appear later in the course.</p><p>69 persons who had laboratory indications of early or overt tissue deficiency of vitamin B12 or folate and who had no ongoing vitamin treatment were given cobalamin for six months. Those whose MMA or tHcy levels did not normalise were given folic acid in addition to cobalamin. After further treatment for three months, all persons but one had normal levels. The laboratory effect still remained after three years of treatment. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings.</p><p><b>Conclusion:</b> A substantial proportion of elderly persons have laboratory signs of incipient tissue deficiency of vitamin B12 and folate. Treatment normalises lab parameters and some symptoms.</p>

The principal aim has been to investigate the contemporary role and importance of edible wild plants in the diets of women in different agro-ecological regions of Vietnam. Field studies were undertaken in four villages in the Mekong Delta (MD) and the Central Highlands (CH) in 1995-1999. Data collection included rapid appraisal techniques, botanical identification, dietary assessments (7-day food frequency recall), anthropometry, blood sampling (haemoglobin, serum ferritin, serum retinol and C-reactive protein) and analysis of vegetable samples (dry matter, selected minerals and vitamins, tannins and phytic acid). A food variety analysis was used to test the adequacy of diets. The uses of over 90 wild plant species were documented, many with multiple functions as foods, medicines and livestock feeds. In the dietary assessment 29 species were reported. Most women used a combination of home produced, commercial and wild vegetables. A high 72 and 43% respectively of the vegetables consumed in the MD and CH sites were gathered (rainy season). They contributed significantly to micronutrient intakes, especially vitamin A, calcium, vitamin C and folate. They added considerably to food diversity and women with the most diverse diets had relatively adequate nutrient intakes. The species used and importance of wild plants varied considerably with region, season and ethnicity. The main conclusions are that edible wild plants continue to make important contributions to the nutrient intakes of women. If this is neglected in diet assessments our understanding of the overall dietary adequacy may be misinterpreted and much valuable knowledge of traditional food diversification may be lost. A food variety analysis can be a useful tool in identifying groups with inadequate diets. The dual role of many species as dietary components and in preventive health care deserves greater attention.

Cobalamin (vitamin B12) is one of several essential micronutrients needed by the human organism. Other important micronutritients, which interplay with vitamin B12, are folate and iron. During the last ten years, the attention has been drawn to different forms of neurological disorders supposed to be caused by vitamin B12 deficiency. Vitamin B12 deficiency states are common among elderly patients in primary health care and sometimes in hospital care, especially in geriatric practice. This is a study to define the cobalamin treatment traditions, among Swedish physicians in the period 1990 – 2000. The period was distinguished by an intense debate on the issue by the physicians, an increase of cobalamin consumption, and a shift from parenteral therapy towards oral high-dose therapy. It had been known that symptoms of cobalamin deficiency could start in the nervous system. This knowledge was reinforced by the application of homocysteine and methyl-malonic acid (MMA) in deficiency diagnosis. Introduction of homocysteine and MMA in deficiency diagnosis changed the view on deficiency prevalence, by identifying persons at risk to develop B12 deficiency prior to established symptoms. In this study, Swedish physicians are regarded mainly as receivers of communication about the markers homocysteine and MMA, and deficiency states of cobalamin and folate. The main senders were scientists from North America, Norway, Denmark, and Sweden. This study sets the senders and the receivers of cobalamin communication on a collegial level and quantifies and evaluates the feed-back from the receivers. The receivers, gen¬eral practitioners and geriatricians, appeared to be familiar with old knowledge and frontier concepts in the field. Thus, it is suggested that the increase of B12 prescriptions in Sweden 1990 – 2000 reflected an increased awareness of B12-associated clinical problems among the physicians managing the majority of deficiency patients, although a possible overconsumption of pharmaceutical drugs must be kept in mind.

Background Colorectal cancer (CRC) is the second most common malignancy in developed countries. The mortality is high, with nearly half of patients dying from the disease. The primary treatment of CRC is surgery, and decisions about additional treatment with chemotherapy are based mainly on tumor stage. Novel prognostic markers that identify patients at high risk of recurrence and cancer-related death are needed. The development of CRC has been described in terms of two different pathways; the microsatellite instability (MSI) and chromosomal instability (microsatellite stable, MSS) pathway. More recently, the CpG island methylator phenotype (CIMP), characterized by frequent DNA hypermethylation, has been described as an alternative pathway of tumorigenesis. The event of DNA methylation is dependent on one-carbon metabolism, in which folate and vitamin B12 have essential functions. The purpose of this thesis was to study CIMP in CRC. The specific aims were to investigate the potential role of components of one-carbon metabolism as risk factors for this subgroup of tumors, and the prognostic importance of CIMP status, taking into consideration important confounding factors, such as MSI and tumor-infiltrating T cells. Methods CRC cases and referents included in the Northern Sweden Health and Disease Study (NSHDS, 226 cases and 437 referents) and CRC cases in the Colorectal Cancer in Umeå Study (CRUMS, n=490) were studied. Prediagnostic plasma concentrations of folate and vitamin B12 were analyzed in NSHDS. In both study groups, CIMP status was determined in archival tumor tissue by real-time quantitative PCR using an eight-gene panel (CDKN2A, MLH1, CACNA1G, NEUROG1, RUNX3, SOCS1, IGF2 and CRABP1). MSI screening status and the density of tumor-infiltrating T cells were determined by immunohistochemistry.  Results An inverse association was found between plasma concentrations of vitamin B12 and rectal, but not colon, cancer risk. We also found a reduced risk of CIMP-high and CIMP-low CRC in study subjects with the lowest levels of plasma folate. We found that patients with CIMP-low tumors in both NSHDS and CRUMS had a poorer prognosis compared with CIMP-negative, regardless of MSI screening status. We also found that MSS CIMP-high patients had a poorer prognosis compared with MSS CIMP-negative. The density of tumor-infiltrating T cells and CIMP status were both found to be independent predictors of CRC patient prognosis. A particularly poor prognosis was found in patients with CIMP-low tumors poorly infiltrated by T cells. In addition, the density of T cells appeared to be more important than MSI screening status for predicting CRC patient prognosis. Conclusion Rather than being one disease, CRC is a heterogeneous set of diseases with respect to clinico-pathological and molecular characteristics. We found that the association between risk and plasma concentration of vitamin B12 and folate depends on tumor site and CIMP status, respectively. Patient prognosis was found to be different depending on CIMP and MSI screening status, and the density of tumor-infiltrating T cells.

The aims of this study were to document the levels of cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) in serum and their relations to symptoms, clinical findings, and other factors in order to improve the possibilities of detecting early deficiency of vitamin B12 or folate, and to study the effects of cobalamin and folic acid treatment over a three-year period. The study population consisted of a 20% random sample of persons 70 years or older living in Älvkarleby in mid-Sweden. They were invited to a survey and 224 (88.4%) persons responded. Data were obtained by questionnaire, laboratory investigations and physical examination for the period 1993 – 1999. In a multivariate analysis performed at baseline, serum MMA and tHcy were significantly and independently correlated to age, serum cobalamin, and creatinine levels, and tHcy also to sex and serum folate. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin or mean red cell volume. Almost half of the study population had signs of low tissue levels of vitamin B12 or folate. Among those who took multivitamin preparations, the proportion was much lower, 25%. Among traditional symptoms and clinical findings that have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis were significantly associated with abnormal serum folate and tHcy levels. Traditional symptoms of vitamin deficiency may appear later in the course. 69 persons who had laboratory indications of early or overt tissue deficiency of vitamin B12 or folate and who had no ongoing vitamin treatment were given cobalamin for six months. Those whose MMA or tHcy levels did not normalise were given folic acid in addition to cobalamin. After further treatment for three months, all persons but one had normal levels. The laboratory effect still remained after three years of treatment. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings. Conclusion: A substantial proportion of elderly persons have laboratory signs of incipient tissue deficiency of vitamin B12 and folate. Treatment normalises lab parameters and some symptoms.

Myc transcriptionally regulates genes involved in processes such as cell proliferation, metabolism, differentiation, and angiogenesis.  MYC expression is deregulated in many types of human cancer; therefore discovering the mechanisms behind MYCs role in tumorigenesis is essential.  In this dissertation, I have focused on several Myc target genes, Spermidine synthase (Srm); Lactate dehydrogenase (Ldh); 3-phosphoglycerate dehydrogenase (Phgdh); Serine hydroxymethyltransferase (SHMT) 1 and 2; and Pim-3 (a member of the Pim family of serine/threonine kinases).  These enzymes play a role in various functions: Spermidine synthase (polyamine synthesis); Lactate dehydrogenase (glycolysis); Phgdh and Shmt (serine metabolism); and Pim-3 (cell signaling).  In order to elucidate the impact Myc over-expression has on metabolism in tumorigenesis, we use human cell lines, and transgenic mice as well as cell lines and tissues derived from these mice.  The impact of inhibition of these target genes on Myc-driven tumorigenesis was done by genetically inhibiting the target gene (using RNAi or mouse models) or inhibiting the protein with a chemical inhibitor.  Investigating these Myc target genes will help determine if inhibition of Myc target genes is a viable approach for chemotherapeutics, and under what conditions this inhibition may be the most valuable.  In paper I, we examine SRM; a highly expressed enzyme in the polyamine synthesis pathway that converts putrescine to spermidine, and is important for actively growing cells.  Genetic inhibition via RNAi against Srm, or chemical inhibition of Srm, resulted in decreased proliferation of B-cell tumor lines from transgenic mice in vitro.  In vivo treatment of λ-Myc transgenic mice with a chemical SRM inhibitor exhibited a significant chemopreventative effect on tumor formation. These results support previous findings that inhibition of polyamine synthesis pathway enzymes has a place in cancer therapy.  Many Myc target genes have been suggested as attractive targets in battling Myc-driven tumorigenesis.  Surprisingly in paper II, when we analyzed the inhibition of other Myc target genes, such as Ldh, Shmt, and Phgdh, we found that inhibition of these genes did not inhibit Myc-driven tumorigenesis to any significant degree. However, inhibition of Ldh, Phgdh and Shmt2 had a notable effect on in vitro Ras-driven transformation.  These findings suggest that chemotherapeutic inhibition of metabolic genes such as Ldh, Phgdh and Shmt2 may be effective in genetically defined settings, keeping in mind the oncogenic lesion behind the tumor.  The Pim kinase family consists of three serine/threonine kinases, Pim1-3.  In paper III, we found that Pim-3 is a direct Myc target gene and that Pim-3 expression is high in Burkitt Lymphoma samples taken from human patients, as well as spontaneously arising lymphomas from Myc transgenic mice. We also found that inhibition of Pim-3 using a pan-Pim kinase inhibitor, Pimi, in these spontaneously arising Myc lymphomas resulted in caspase independent cell death.  These results indicate that Pim kinase inhibition may be a potential chemotherapeutic strategy in human lymphomas that rely on Pim-3 kinase expression.

O dano genético pode ocorrer espontaneamente sob circunstâncias metabólicas normais e pode ser potencializado em situações de deficiência dietética e exposição excessiva a mutagênicos e carcinogênicos ambientais. As deficiências de ácido fólico, vitamina B6 e vitamina B12 podem levar a um aumento nos níveis e alterações na metilação do DNA. MTHFR é a enzima chave na via de metabolização do folato e o polimorfismo MTHFR C677T conduz à redução na atividade da enzima. O objetivo deste estudo foi avaliar influências da ingestão dos micronutrientes B12, B6 e folato (B9), do polimorfismo MTHFR C677T na instabilidade genômica de indivíduos expostos ocupacionalmente a pesticidas. O estudo envolveu 69 homens e 41 mulheres (n= 110) com uma idade média 42,3 ± 13,32 anos no qual 42 (38,2%) deles apresentaram peso normal, 51 (46,4%) sobrepeso e 15 (13,6%) obesidade grau I, todos os indivíduos da amostra são fumicultores de Venâncio Aires e Santa Cruz do Sul (estado do Rio Grande do Sul, Brasil). A genotipagem do polimorfismo MTHFR C677T foi realizada pelo método PCR-RFLP. Os dados de dano de DNA foram avaliados pelos biomarcadores de exposição ocupacional ensaio cometa e micronúcleo. O status nutricional foi avaliado com base na média de 3 recordatórios de 24 horas (coletados em 3 dias não consecutivos , incluindo um final de semana em um intervalo de 4 meses). A ingestão dos micronutrientes foi estimada usando o programa nutricional Food Processor SQL 10.9. Não foram encontradas diferenças significativas entre idade e tempo de exposição a pesticidas para os parâmetros analisados. Encontramos aumento na frequência de micronúcleo de linfócitos em indivíduos com ingestão inadequada de folato e vitamina B12, apresentando diferença significativa (P = 0,030) e (P = 0,014) respectivamente quando comparados com os indivíduos com ingestão adequada. Dano de DNA não mostrou resultados significativos quando relacionados com tabagismo, anos de exposição, IMC e polimorfismo MTHFR C677T. A correlação entre dano do DNA, ingestão de folato, B6 e B12 e o polimorfismo MTHFR não apresentou significância. Em conclusão, nossos resultados indicaram que a adequação de folato para valores ≥ 320 μg /dia e vitamina B12 ≥ 2,0 μg /dia, nesta amostra exposta, estaria protegendo da ação mutagênica dos pesticidas. A dieta adequada, tanto em folato quanto em vitamina B12 poderia estar auxiliando em um reparo de DNA adequado sugerindo um fator de proteção nesses indivíduos. / Genetic damage can occur spontaneously under normal metabolic circumstances and can also be present in situations of dietary deficiency or inadequate intake of nutrients and excessive exposure to environmental mutagens. The purpose of this study was to evaluate the influence of the intake of micronutrients B12, B6 and folate and of polymorphism MTHFR C677T in the induction of DNA damage in individuals exposed to pesticides. The study involved 69 men and 41 women who were tobacco farmers in the region of Venâncio Aires (State of Rio Grande do Sul, Brasil). DNA damage was analyzed by the Comet Test and Micronucleus Test (MN); dietary intake was evaluated based on the mean of three 24-hour Diet Recall questionnaires. The nutrient intake data were computerized and estimated in the Food Processor SQL 10.9 program. The DNA damage results showed a significant increase in MN frequency in the lymphocytes of individuals who had an inadequate intake of folate and B12 (P = 0.030 and P = 0.014, respectively). No significant association was found between DNA damage and polymorphism MTHFR C677T. Correlations between DNA damage and polymorphism MTHFR C677T and nutrient intake were not significant. In conclusion, our results indicated that the adequate intake of folate (≥ 320 μg /day) and vitamin B12 (≥ 2,0 μg /day) can provide protection from the mutagenic action of pesticides. A dietary adaptation of folate and B12 can ensure adequate repair, showing that diet is a protective factor in this population.

O dano genético pode ocorrer espontaneamente sob circunstâncias metabólicas normais e pode ser potencializado em situações de deficiência dietética e exposição excessiva a mutagênicos e carcinogênicos ambientais. As deficiências de ácido fólico, vitamina B6 e vitamina B12 podem levar a um aumento nos níveis e alterações na metilação do DNA. MTHFR é a enzima chave na via de metabolização do folato e o polimorfismo MTHFR C677T conduz à redução na atividade da enzima. O objetivo deste estudo foi avaliar influências da ingestão dos micronutrientes B12, B6 e folato (B9), do polimorfismo MTHFR C677T na instabilidade genômica de indivíduos expostos ocupacionalmente a pesticidas. O estudo envolveu 69 homens e 41 mulheres (n= 110) com uma idade média 42,3 ± 13,32 anos no qual 42 (38,2%) deles apresentaram peso normal, 51 (46,4%) sobrepeso e 15 (13,6%) obesidade grau I, todos os indivíduos da amostra são fumicultores de Venâncio Aires e Santa Cruz do Sul (estado do Rio Grande do Sul, Brasil). A genotipagem do polimorfismo MTHFR C677T foi realizada pelo método PCR-RFLP. Os dados de dano de DNA foram avaliados pelos biomarcadores de exposição ocupacional ensaio cometa e micronúcleo. O status nutricional foi avaliado com base na média de 3 recordatórios de 24 horas (coletados em 3 dias não consecutivos , incluindo um final de semana em um intervalo de 4 meses). A ingestão dos micronutrientes foi estimada usando o programa nutricional Food Processor SQL 10.9. Não foram encontradas diferenças significativas entre idade e tempo de exposição a pesticidas para os parâmetros analisados. Encontramos aumento na frequência de micronúcleo de linfócitos em indivíduos com ingestão inadequada de folato e vitamina B12, apresentando diferença significativa (P = 0,030) e (P = 0,014) respectivamente quando comparados com os indivíduos com ingestão adequada. Dano de DNA não mostrou resultados significativos quando relacionados com tabagismo, anos de exposição, IMC e polimorfismo MTHFR C677T. A correlação entre dano do DNA, ingestão de folato, B6 e B12 e o polimorfismo MTHFR não apresentou significância. Em conclusão, nossos resultados indicaram que a adequação de folato para valores ≥ 320 μg /dia e vitamina B12 ≥ 2,0 μg /dia, nesta amostra exposta, estaria protegendo da ação mutagênica dos pesticidas. A dieta adequada, tanto em folato quanto em vitamina B12 poderia estar auxiliando em um reparo de DNA adequado sugerindo um fator de proteção nesses indivíduos. / Genetic damage can occur spontaneously under normal metabolic circumstances and can also be present in situations of dietary deficiency or inadequate intake of nutrients and excessive exposure to environmental mutagens. The purpose of this study was to evaluate the influence of the intake of micronutrients B12, B6 and folate and of polymorphism MTHFR C677T in the induction of DNA damage in individuals exposed to pesticides. The study involved 69 men and 41 women who were tobacco farmers in the region of Venâncio Aires (State of Rio Grande do Sul, Brasil). DNA damage was analyzed by the Comet Test and Micronucleus Test (MN); dietary intake was evaluated based on the mean of three 24-hour Diet Recall questionnaires. The nutrient intake data were computerized and estimated in the Food Processor SQL 10.9 program. The DNA damage results showed a significant increase in MN frequency in the lymphocytes of individuals who had an inadequate intake of folate and B12 (P = 0.030 and P = 0.014, respectively). No significant association was found between DNA damage and polymorphism MTHFR C677T. Correlations between DNA damage and polymorphism MTHFR C677T and nutrient intake were not significant. In conclusion, our results indicated that the adequate intake of folate (≥ 320 μg /day) and vitamin B12 (≥ 2,0 μg /day) can provide protection from the mutagenic action of pesticides. A dietary adaptation of folate and B12 can ensure adequate repair, showing that diet is a protective factor in this population.

A metilação do DNA é uma alteração epigenética que atua na regulação da expressão gênica. A deficiência de vitaminas (cobalamina, B6 e folato) pode interferir na taxa de metilação. O efeito da deficiência destas vitaminas foi determinado em estudos com cultura de células e em animais. No entanto, são raros os estudos realizados com seres humanos. Os objetivos deste trabalho foram: avaliar a taxa de metilação do DNA de leucócitos na região promotora dos genes Interferon gama (IFN&#947;), Serpin B5 e Stratifin; verificar se existe associação entre as concentrações das vitaminas e dos metabólitos com a taxa de metilação do DNA dos 3 genes; e analisar quais são os fatores de predição para a taxa de metilação do DNA (variável dependente) considerando como variáveis independentes os valores séricos das vitaminas e metabólitos, em mulheres com idades gestacionais de 16, 28 e 36 semanas. Cento e oitenta e três mulheres foram convidadas a participar desse estudo, porém apenas 96 completaram o estudo prospectivo. Foram determinadas as concentrações séricas da cobalamina (Cbl), folato, vitamina B6, S-adenosilmetionina (SAM), S-adenosilhomocisteína (SAH), ácido metilmalônico (MMA), homocisteína total (tHcy) e folato eritrocitário. A taxa de metilação nos 3 genes foi determinada por qMSP (Quantitative Methylation Specific - Polimerase Chain Reaction). Várias mulheres estavam fazendo uso de suplementação com ácido fólico e/ou polivitamínicos. Diante deste fato foram formados 4 subgrupos: Grupo 1 (constituído por mulheres que não usaram suplementação), Grupo 2 (mulheres que usaram suplementação em todas as idades gestacionais estudadas - 16, 28 e 36 semanas), Grupo 3 (mulheres que usaram suplementação no início da gestação até a 16ª semana) e Grupo 4 (mulheres que usaram suplementação na 16ª e 28ª semana gestacional). Não houve diferença entre as taxas de metilação do DNA dos genes IFN&#947;, Serpin B5 e Stratifin durante o período gestacional estudado. As taxas de metilação no gene IFN&#947; do grupo 1 foram maiores, quando comparadas as taxas dos demais grupos. Em modelos de regressão linear múltipla, considerando o período gestacional como um todo, apenas a vitamina B6 e a tHcy foram diretamente associadas aos valores da taxa de metilação do gene IFN&#947;. No entanto, a vitamina B6 foi inversamente associada, enquanto que tHcy esteve diretamente associada aos valores da taxa de metilação do gene Stratifin. A taxa de metilação não sofre alterações durante a gestação; a vitamina B6 e a tHcy foram os fatores de predição para as taxas de metilação do DNA na região promotora dos genes IFN&#947; e Stratifin. / DNA methylation is an epigenetic modification that regulates gene expression. Cobalamin, vitamin B6 and folate deficiencies can impair the DNA methylation index. Studies involving cultured cells and animals have evaluated the effect of vitamin deficiencies in DNA methylation. However, few studies were conducted in humans. The goals of this study were: to evaluate the leukocyte DNA methylation index in the promoter region of interferon gamma (IFN&#947;), Serpin B5 and Stratifin genes; to assess the association between vitamins and metabolites concentrations and DNA methylation index in three genes; and to examine the predictive factors for DNA methylation index using as independent variables: serum folate, serum cobalamin, serum vitamin B6, erythrocyte folate, methylmalonic acid (MMA), total homocysteine (tHcy) in three gestational ages (16th, 28th and 36,th weeks). A hundred eighty three women were included, but only 96 completed the prospective study. The serum concentrations of cobalamin, folate, vitamin B6, S-adenosylmethionine (SAM), Sadenosylhomocysteine (SAH), MMA, tHcy were determined. The erythrocyte folate concentration was also evaluated. The DNA methylation index was determined in three genes by qMSP (Quantitative Methylation Specific - Polymerase Chain Reaction). Several women were taking folic acid supplementation and/or multivitamins. Four groups were formed according to supplementation use: Group 1 (women who take no supplementation), Group 2 (women who took supplements at 16th, 28th and 36th weeks of pregnancy), Group 3 (women who took supplements in early pregnancy and up to 16 weeks) and Group 4 (women who took supplements in the 16th and 28th week of pregnancy). There was no difference between the DNA methylation index in the IFN&#947;, Serpin B5 and Stratifin genes during the gestational periods studied. The DNA methylation index in the IFN&#947; gene in group 1 was higher than those indexes from other groups. In multiple linear regression models considering the gestational periods as a whole, only vitamin B6 and tHcy were directly associated to DNA methylation index in IFN&#947; gene. However, vitamin B6 was inversely associated, whereas tHcy was directly associated with values of DNA methylation in Stratifin. The DNA methylation index does not change during pregnancy, vitamin B6 and tHcy were the predictors of DNA methylation in the promoter region of IFN&#947; and Stratifin genes.

O dano genético pode ocorrer espontaneamente sob circunstâncias metabólicas normais e pode ser potencializado em situações de deficiência dietética e exposição excessiva a mutagênicos e carcinogênicos ambientais. As deficiências de ácido fólico, vitamina B6 e vitamina B12 podem levar a um aumento nos níveis e alterações na metilação do DNA. MTHFR é a enzima chave na via de metabolização do folato e o polimorfismo MTHFR C677T conduz à redução na atividade da enzima. O objetivo deste estudo foi avaliar influências da ingestão dos micronutrientes B12, B6 e folato (B9), do polimorfismo MTHFR C677T na instabilidade genômica de indivíduos expostos ocupacionalmente a pesticidas. O estudo envolveu 69 homens e 41 mulheres (n= 110) com uma idade média 42,3 ± 13,32 anos no qual 42 (38,2%) deles apresentaram peso normal, 51 (46,4%) sobrepeso e 15 (13,6%) obesidade grau I, todos os indivíduos da amostra são fumicultores de Venâncio Aires e Santa Cruz do Sul (estado do Rio Grande do Sul, Brasil). A genotipagem do polimorfismo MTHFR C677T foi realizada pelo método PCR-RFLP. Os dados de dano de DNA foram avaliados pelos biomarcadores de exposição ocupacional ensaio cometa e micronúcleo. O status nutricional foi avaliado com base na média de 3 recordatórios de 24 horas (coletados em 3 dias não consecutivos , incluindo um final de semana em um intervalo de 4 meses). A ingestão dos micronutrientes foi estimada usando o programa nutricional Food Processor SQL 10.9. Não foram encontradas diferenças significativas entre idade e tempo de exposição a pesticidas para os parâmetros analisados. Encontramos aumento na frequência de micronúcleo de linfócitos em indivíduos com ingestão inadequada de folato e vitamina B12, apresentando diferença significativa (P = 0,030) e (P = 0,014) respectivamente quando comparados com os indivíduos com ingestão adequada. Dano de DNA não mostrou resultados significativos quando relacionados com tabagismo, anos de exposição, IMC e polimorfismo MTHFR C677T. A correlação entre dano do DNA, ingestão de folato, B6 e B12 e o polimorfismo MTHFR não apresentou significância. Em conclusão, nossos resultados indicaram que a adequação de folato para valores ≥ 320 μg /dia e vitamina B12 ≥ 2,0 μg /dia, nesta amostra exposta, estaria protegendo da ação mutagênica dos pesticidas. A dieta adequada, tanto em folato quanto em vitamina B12 poderia estar auxiliando em um reparo de DNA adequado sugerindo um fator de proteção nesses indivíduos. / Genetic damage can occur spontaneously under normal metabolic circumstances and can also be present in situations of dietary deficiency or inadequate intake of nutrients and excessive exposure to environmental mutagens. The purpose of this study was to evaluate the influence of the intake of micronutrients B12, B6 and folate and of polymorphism MTHFR C677T in the induction of DNA damage in individuals exposed to pesticides. The study involved 69 men and 41 women who were tobacco farmers in the region of Venâncio Aires (State of Rio Grande do Sul, Brasil). DNA damage was analyzed by the Comet Test and Micronucleus Test (MN); dietary intake was evaluated based on the mean of three 24-hour Diet Recall questionnaires. The nutrient intake data were computerized and estimated in the Food Processor SQL 10.9 program. The DNA damage results showed a significant increase in MN frequency in the lymphocytes of individuals who had an inadequate intake of folate and B12 (P = 0.030 and P = 0.014, respectively). No significant association was found between DNA damage and polymorphism MTHFR C677T. Correlations between DNA damage and polymorphism MTHFR C677T and nutrient intake were not significant. In conclusion, our results indicated that the adequate intake of folate (≥ 320 μg /day) and vitamin B12 (≥ 2,0 μg /day) can provide protection from the mutagenic action of pesticides. A dietary adaptation of folate and B12 can ensure adequate repair, showing that diet is a protective factor in this population.