ABSTRACT
Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.(AU)
Subject(s)
Humans , Male , Adult , Female , Middle Aged , Aged , DNA Methylation , Stomach Neoplasms/genetics , DNA Mismatch Repair , Sequence Analysis, DNA , Brazil , DNA Repair Enzymes/genetics , Promoter Regions, GeneticABSTRACT
Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.
Subject(s)
Humans , Male , Adult , Female , Middle Aged , DNA Methylation , Stomach Neoplasms/genetics , DNA Mismatch Repair , Sequence Analysis, DNA , Brazil , DNA Repair Enzymes/genetics , Promoter Regions, GeneticABSTRACT
The collared peccary (Tayassu tajacu) is widely distributed over the American continent, being found from the south of the USA to the north of Argentina.In Brazil, it is spread all over the country, being one of the potential species to be raised in captivity. Therefore, the cytogenetic techniques could be a potencial tool for reproductive monitoring of animals raised in captivity, mainly when destined for commercial purposes. This study had the objective of determining the chromosome number of two populations raised in captivity and characterizing them by GTG banding. For this purpose, an analysis was made of mitotic metaphases obtained from lymphocyte cultures made from blood samples of 11 animals, six of which from the Northeast and five from the North of Brazil. The results of this analysis showed the same ka ryotype pattern for the species (2n=30 chromosomes and NF=48), besides corresponding to the South American pattern of the species, i.e., without a translocation between autosomes 1 and 8, chromosome X acrocentric, and no differences were found between the two populations studied. However, chromosomal polymorphisms were observed compared to data from the literature on populations from North and South America.(AU)
Subject(s)
Male , Animals , Artiodactyla/genetics , Chromosomes, Mammalian/genetics , Karyotyping , X Chromosome , Y Chromosome , BrazilABSTRACT
Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.(AU)
Subject(s)
Humans , Male , Adolescent , Adult , Female , Comet Assay , Cells, Cultured , Lymphocytes , Mutagens/pharmacology , Physalis/toxicity , Micronucleus Tests , Plant Extracts/toxicityABSTRACT
The collared peccary (Tayassu tajacu) is widely distributed over the American continent, being found from the south of the USA to the north of Argentina.In Brazil, it is spread all over the country, being one of the potential species to be raised in captivity. Therefore, the cytogenetic techniques could be a potencial tool for reproductive monitoring of animals raised in captivity, mainly when destined for commercial purposes. This study had the objective of determining the chromosome number of two populations raised in captivity and characterizing them by GTG banding. For this purpose, an analysis was made of mitotic metaphases obtained from lymphocyte cultures made from blood samples of 11 animals, six of which from the Northeast and five from the North of Brazil. The results of this analysis showed the same ka ryotype pattern for the species (2n=30 chromosomes and NF=48), besides corresponding to the South American pattern of the species, i.e., without a translocation between autosomes 1 and 8, chromosome X acrocentric, and no differences were found between the two populations studied. However, chromosomal polymorphisms were observed compared to data from the literature on populations from North and South America.
Subject(s)
Male , Animals , Artiodactyla/genetics , Chromosomes, Mammalian/genetics , Karyotyping , Brazil , X Chromosome , Y ChromosomeABSTRACT
Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.
Subject(s)
Humans , Male , Adolescent , Adult , Female , Cells, Cultured , Comet Assay , Lymphocytes , Mutagens/pharmacology , Physalis/toxicity , Plant Extracts/toxicity , Micronucleus TestsABSTRACT
Fibroadenoma (FA) is a benign breast tumour that occurs in about 25% of women. Cytogenetic studies suggest that numerical chromosomal aberrations may contribute to tumorigenesis, but chromosomal instability is still poorly characterised in breast cancer. The aim of this study was to investigate numerical alterations of chromosome 21 in 15 breast FAs. All samples were analysed by classical cytogenetics and by fluorescence in situ hybridisation (FISH) for chromosome 21 DNA sequences. Classical cytogenetics analysis showed that all cells were diploidies with modal number varying between 43 and 47 chromosomes, and clonal chromosome alterations in 46.7% of tumours. Clonal numerical alterations involved, preferentially, chromosomes 8, 10, 12, 16 and 21. FISH analysis showed a statistically significant difference for chromosome 21 monosomy between seven samples and control group. This monosomy varied from 24.5% to 43.5% of analysed cells. The presence of chromosomal alterations in FAs may be a consequence of the proliferation process and is probably not related to the aetiology of this type of lesion. The study of benign proliferations and comparison with chromosome alterations in their malignant counterparts should result in an understanding of the genes acting in cell proliferation alone and those that cause these cells to both undergo malignant transformation and become invasive.
Subject(s)
Aneuploidy , Breast Neoplasms/genetics , Chromosomes, Human, Pair 21/genetics , Fibroadenoma/genetics , In Situ Hybridization, Fluorescence , Adolescent , Adult , Cytogenetic Analysis , Female , Humans , Monosomy , Statistics as TopicABSTRACT
Gastric cancer is the third most frequent type of neoplasia and the second most important cause of death in the world. ACP01 is the first gastric adenocarcinoma cell line developed in Brazil. To evaluate chromosomal aberrations implicated in gastric carcinogenesis, we analysed three different passages (6th, 12th and 35th) of ACP01 cell line by fluorescence in situ hybridisation using chromosome 8 alpha-satellite probe. Most of the chromosome 8 alterations found involved a numerical increase of this chromosome. Chromosome 8 trisomy was detected in all cases, varying from 37% (6th passage) to 67% (35th passage), and chromosome 8 tetrasomy (also observed in all passages) varied from 2.5% (6th passage) to 30% (35th passage). The presence of five signals for chromosome 8 was observed in all passages with the highest frequency found in the 12th passage (20%). Our results confirm that trisomy of chromosome 8 is a common biological phenomenon in adenocarcinoma of stomach and can be used as a gastric mucosa malignancy marker. Although gastric tumours are frequent neoplasias, papers on their cytogenetics are scarce in the literature. It is, therefore, necessary to conduct new studies aiming to identify peculiar genetic characteristics of a tumour, which might help in diagnosis and prognosis of this disease, besides allowing more accurate therapeutic conduct to be established.
