ABSTRACT
The human leukocyte antigen-E (HLA-E) locus is a human major histocompatibility complex (MHC) gene associated with immune-modulation and suppression of the immune response by the interaction with specific natural killer (NK) and T cell receptors (TCRs). It is considered one of the most conserved genes of the human MHC; however, this low nucleotide variability seems to be a consequence of the scarce number of studies focusing on this subject. In this manuscript we assessed the nucleotide variability at the HLA-E coding and 3' untranslated regions (3'UTRs) in Brazil and in the populations from the 1000Genomes Consortium. Twenty-eight variable sites arranged into 33 haplotypes were detected and most of these haplotypes (98.2%) are encoding one of the two HLA-E molecules found worldwide, E*01:01 and E*01:03. Moreover, three worldwide spread haplotypes, associated with the coding alleles E*01:01:01, E*01:03:01 and E*01:03:02, account for 85% of all HLA-E haplotypes, suggesting that they arose early before human speciation. In addition, the low nucleotide diversity found for the HLA-E coding and 3'UTR in worldwide populations suggests that the HLA-E gene is in fact a conserved gene, which might be a consequence of its key role in the modulation of the immune system.
Subject(s)
3' Untranslated Regions , Haplotypes , Histocompatibility Antigens Class I/classification , Histocompatibility Antigens Class I/genetics , Open Reading Frames , Polymorphism, Genetic , Alleles , Base Sequence , Brazil , Conserved Sequence , Genetic Speciation , Histocompatibility Antigens Class I/immunology , Humans , Molecular Sequence Data , Phylogeny , HLA-E AntigensABSTRACT
We report a novel nonclassical class I HLA-E*01:06 allele observed in Brazilian individuals.
Subject(s)
Alleles , HLA-DQ beta-Chains/genetics , Mutation , Base Sequence , Brazil , Exons , Female , Histocompatibility Testing , Humans , Male , Molecular Sequence Data , Sequence Alignment , Sequence Analysis, DNAABSTRACT
Here we report two new non-classical class I HLA-G alleles found in the Brazilian population.
Subject(s)
Alleles , Exons/genetics , HLA-G Antigens/genetics , Mutation/genetics , Base Sequence , Brazil , Female , Humans , Male , Molecular Sequence Data , Polymorphism, Single Nucleotide , Sequence Analysis, DNAABSTRACT
Mutagenic and antimutagenic activities of the medicinal plant Duguetia furfuracea were assessed using SMART/wing and ring-X-loss tests. For the ring-X-loss test, 2- to 3-day-old Drosophila melanogaster ring-X-lineage males and virgin ywsn³ females received D. furfuracea infusion at doses of 0.085, 0.042, or 0.014 g/mL for 24 h. We found that D. furfuracea did not produce any mutagenic effects in D. melanogaster germinative cells. The somatic cells of D. melanogaster were analyzed using the SMART/wing test involving three lineages - mwh, flr³, and ORR - and the same doses of D. furfuracea infusion employed in the ring-X-loss test, as well as 20 mM urethane. The results of both standard (ST) and high bioactivation (HB) crosses showed absence of mutagenic activity of D. furfuracea. In contrast, in both ST and HB crosses, we observed a modulatory effect of D. furfuracea against the genotoxic activity of urethane.
Subject(s)
Annonaceae/chemistry , Drosophila melanogaster/drug effects , Drosophila melanogaster/genetics , Plant Extracts/pharmacology , Animals , Drosophila melanogaster/cytology , Female , Genotype , Male , Mutagenicity Tests , Mutagens/pharmacology , Mutation , Phenotype , Plants, Medicinal/chemistry , Wings, Animal/drug effectsABSTRACT
Luehea divaricata is a native plant of the Brazilian Cerrado, known as "açoita-cavalo". It is used as a popular herbal medicine in the treatment of dysentery, bleeding, arthritis, tumors, ulcers, and gangrenous wounds. Considering that herbal medicines sometimes provoke tumors and/or may prevent mutational events, it is important to study the action of these natural drugs on DNA. Aqueous extract of the bark of L. divaricata was evaluated at three different concentrations (0.10, 0.30, 0.50 mg/mL), individually and in combination with the neoplastic drug doxorubicin (DXR), by the somatic mutation and recombination test (SMART/wing) in Drosophila melanogaster. Distilled water was included as a negative control. The mutation frequency in the treatments with L. divaricata extract alone was not significantly higher than in the negative control for standard (ST) and high bioactivation (HB) crosses. When L. divaricata extract was combined with DXR, there was a significant reduction in the frequency of spots when compared to DXR alone, in both crosses. Further studies with other experimental models would be useful to confirm that L. divaricata extract is not harmful and that it could be used in the prevention of cancer.
Subject(s)
Drosophila melanogaster/drug effects , Malvaceae/chemistry , Mutagens/toxicity , Plant Extracts/toxicity , Plants, Medicinal/toxicity , Animals , Doxorubicin/pharmacology , Drosophila melanogaster/genetics , Mutagenicity Tests , Mutation/drug effects , Survival Analysis , Wings, Animal/drug effectsABSTRACT
Palicourea coriacea, popularly known as "douradinha", is a medicinal plant from the Brazilian Cerrado region used in folk medicine to treat kidney and urethral stones and kidney inflammation. We evaluated the cytotoxic, genotoxic, and possible antigenotoxic activities of an aqueous extract of P. coriacea on somatic cells of Drosophila melanogaster, using the somatic mutation and recombination test. We used third-stage larvae of D. melanogaster from a standard cross and a high bioactivation cross and tested 10 different doses of P. coriacea aqueous extract (5, 15, 25, 35, 50, 65, 80, 95, 110, and 125 mg/mL). Doxorubicin (0.125 mg/mL) was used as a positive control and distilled water as a negative control. None of the doses was lethal to the larvae.There was no genotoxic effect at 5, 10, or 15 mg extract/mL. However, a significant decrease in the frequency of spots induced by doxorubicin was observed when administered with P. coriacea aqueous extract at these same doses. We conclude that P. coriacea aqueous extract is not cytotoxic or genotoxic at these doses, but it does protect against the genotoxic action of doxorubicin.
Subject(s)
Doxorubicin/pharmacology , Drosophila melanogaster/drug effects , Drosophila melanogaster/genetics , Rubiaceae/genetics , Rubiaceae/metabolism , Animals , Dose-Response Relationship, Drug , Genes, Plant , Genetic Techniques , Heterozygote , Larva/drug effects , Mutagenicity Tests , Mutation/drug effects , Plant Extracts/pharmacology , Plants, Medicinal , Recombination, Genetic/drug effects , Wings, Animal/drug effectsABSTRACT
Byrsonima verbascifolia, popularly known in Brazil as murici, is a medicinal plant widely used in the treatment of bacterial and viral infections, Chagas's disease, diarrhea, bronchitis, cough and fever, as well as for protection of the intestinal mucosa. Since chemotherapy and radiotherapy, broadly employed in the treatment of cancer, can have undesirable side effects, such as inducing DNA damage in normal cells, it would be useful to investigate compounds that inhibit or reduce these effects. A lyophilized water extract of murici, used at three different concentrations (25, 50, and 100 mg/mL), was tested to determine if it could reduce damage induced by the antineoplastic compound doxorubicin in somatic cells of Drosophila melanogaster, analyzed by SMART/wing. The frequency of mutant spots in descendants from standard and high bioactivation crosses was significantly reduced by treatment with murici extract. Further studies are needed using other experimental models, to determine if murici has the potential to be employed by cancer patients receiving chemotherapy.
