Modulating effect of vitamin D3 on the mutagenicity and carcinogenicity of doxorubicin in Drosophila melanogaster and in silico studies.

Vitamin D3 (VD3) deficiency increases DNA damage, while supplementation may exert a pro-oxidant activity, prevent viral infections and formation of tumors. The aim of this study was to investigate the mutagenicity and carcinogenicity of VD3 alone or in combination with doxorubicin (DXR) using the Somatic Mutation and Recombination Test and the Epithelial Tumor Test, both in Drosophila melanogaster. For better understanding of the molecular interactions of VD3 and receptors, in silico analysis were performed with molecular docking associated with molecular dynamics. Findings revealed that VD3 alone did not increase the frequency of mutant spots, but reduced the frequency of mutant spots when co-administered with DXR. In addition, VD3 did not alter the recombinogenic effect of DXR in both ST and HB crosses. VD3 alone did not increase the total frequency of tumor, but significantly reduced the total frequency of tumor when co-administered with DXR. Molecular modeling and molecular dynamics between calcitriol and Ecdysone Receptor (EcR) showed a stable interaction, indicating the possibility of signal transduction between VD3 and EcR. In conclusion, under these experimental conditions, VD3 has modulatory effects on the mutagenicity and carcinogenicity induced by DXR in somatic cells of D. melanogaster and exhibited satisfactory interactions with the EcR.

Efeito modulador do óleo essencial do limão Taiti (Citrus latifolia) em células somáticas de Drosophila melanogaster / Modulating effect of essential oil of lemon Taiti (Citrus latifolia) on somatic cells of Drosophila melanogaster

Introdução: óleos essenciais são muito utilizados para fins terapêuticos e nas últimas décadas esse interesse tem aumentado exponencialmente devido aos avanços nas terapias naturais. Neste contexto, destaca-se o óleo essencial do limão Taiti, um produto com grande potencial terapêutico e farmacológico. Objetivo: este trabalho objetivou avaliar o efeito carcinogênico e anticarcinogênico do limão Taiti (Citrus latifolia), por meio do teste para detecção de clones de tumores epiteliais em células somáticas de Drosophila melanogaster. Metodologia: larvas de terceiro estágio, do cruzamento entre fêmeas virgens wts/TM3, Sb1 com machos mwh/mwh, foram tratadas cronicamente com diferentes concentrações do óleo essencial do limão Taiti (1,5; 3,0; 6,0 µL) isoladamente e associadas à doxorrubicina (DXR), também foram incluídos dois controles, um negativo (Tween 80 1%) e um positivo (DXR 0,4 mM). Resultados: os resultados revelaram que os indivíduos tratados apenas com as concentrações isoladas do óleo essencial do limão Taiti não apresentaram frequências significativas de tumores quando comparadas ao controle negativo (p>0,05). Contudo, as concentrações associadas apresentaram efeito modulador sobre os danos induzidos pela DXR, pois houve redução significativa (p<0,05) na frequência de tumores, quando comparadas ao controle positivo. Conclusão: o presente trabalho, em condição experimental, atesta que o óleo essencial de limão Taiti (Citrus latifolia) não apresenta ação carcinogênica e sim ação anticarcinogênica em Drosophila melanogaster.

Introduction: essential oils are widely used for therapeutic purposes and in recent decades this interest has increased exponentially due to advances in natural therapies. In this context, the essential oil of lemon Taiti stands out, a product with great therapeutic and pharmacological potential. Objective: this study aimed to evaluate the carcinogenic and anticarcinogenic effect of Tahiti lemon (Citrus latifolia) by testing for clones of epithelial tumors in Drosophila melanogaster somatic cells. Methodology: third stage larvae from crossbreeding wts / TM3, Sb1 virgin females with mwh / mwh males were chronically treated with different concentrations of Taiti lemon essential oil (1.5; 3.0; 6.0 µL) alone and doxorubicin-associated (DXR), two controls were also included, one negative (Tween 80 1%) and one positive (0.4 mM DXR). Results: the results revealed that the individuals treated only with the isolated concentrations of Taiti lemon essential oil did not present significant tumor frequencies when compared to the negative control (p> 0.05). However, the associated concentrations had a modulating effect on DXR-induced damage, since there was a significant reduction (p <0.05) in the frequency of tumors when compared to the positive control. Conclusion: the present work, under experimental condition, attests that Taiti lemon essential oil (Citrus latifolia) did not show carcinogenic action but anticarcinogenic action in Drosophila melanogaster.

Assessment of the carcinogenic potential of high intense-sweeteners through the test for detection of epithelial tumor clones (warts) in Drosophila melanogaster.

High intensity-sweeteners (HIS) are natural or synthetic substances, sweeter than sugar, providing sweetness without calories. Sweeteners are mainly used as an aid in losing weight, preventing obesity and controlling blood sugar levels for diabetics. The objective of this study was to evaluate the carcinogenic potential of the sweeteners aspartame, sucralose, sodium saccharin and steviol glycoside, using the test for detection of epithelial tumor clones in Drosophila melanogaster. Larvae of 72 ± 4h, obtained from wts/TM3 female mated with mwh/mwh males, were treated for approximately 48h with different concentrations of aspartame (0.85, 1.7, 3.4, 6.8 or 13.6 mM ); sucralose (0.5, 1.25, 2.5, 5.0 or 10 mM); sodium saccharin (25; 50; 100; 200 or 400 mM) and steviol glycoside (2.5; 5.0; 10; 20 or 40 mM). Water (Reverse Osmosis) and doxorubicin (DXR 0.4 mM) were used as negative and positive controls, respectively. No statistically significant differences were observed (p > 0.05) in tumor frequencies in individuals treated with all concentrations of these sweeteners when compared to negative control. It was therefore concluded that, in these experimental conditions, aspartame, sucralose, sodium saccharin and steviol glycoside have no carcinogenic effect in D. melanogaster.

Assessment of carcinogenic potential of soft drinks of cola, diet cola, orange and lemon, produced in the city of Uberlândia, Minas Gerais state, Brazil / Avaliação do potencial carcinogênico de refrigerantes à base de cola, diet cola, laranja e limão, produzidos no município de Uberlândia, estado de Minas Gerais, Brasil

Soft drinks are industrialized unfermented beverages, free of alcohol, carbonated, rich in artificial flavors and sugar. The intense consumption of such beverages can be related to not inheritable diseases such as caries, allergy, cellulite and stretch marks, gastrointestinal disorders, diabetes and cancer. The aim of this study was to evaluate the carcinogenic potential of different concentrations of soft drinks produced in the Uberlândia city, Minas Gerais State, Brazil, by means of Epithelial Tumor Detection Test using Drosophila melanogaster as a model. Third stage larvae descendants of crosses between D. melanogaster virgin females wts/TM3, sb¹ and males mwh/mwh were treated with different concentrations (0.83, 1.66 or 3.33 mL/g) of cola, diet cola, orange or lemon soft drinks. The total epithelial tumor rate observed in flies treated with 3.33 mL/g of cola and orange soft drinks was higher than the negative control. The diet cola and lemon caused no significant increase in the overall frequency of epithelial tumors in D. melanogaster. In conclusion, in these experimental conditions, the cola and orange base soft drinks demonstrated carcinogenic potential in somatic cells of D. melanogaster in the concentration of 3.33 mL/g.

Refrigerantes são bebidas industrializadas não fermentadas, livre de álcool, carbonatadas, ricas em aromas artificiais e açúcar. O consumo intenso dessas bebidas pode estar relacionada à doenças não herdáveis como, cáries, quadros alérgicos, formação de celulite e estrias cutâneas, alterações gastrointestinais, diabetes e câncer. O objetivo desse trabalho foi avaliar o potencial carcinogênico de diferentes concentrações de refrigerantes produzidos no município de Uberlândia, Estado de Minas Gerais, Brasil. Foi realizado o Teste de Detecção de Tumor Epitelial em Drosophila melanogaster. Larvas de terceiro estágio descendentes do cruzamento entre fêmeas virgens wts/TM3, sb¹ e machos mwh/mwh de D. melanogaster foram tratadas com diferentes concentrações (0,83; 1,66 ou 3,33 mL/g) de refrigerantes à base de cola, diet cola, laranja e limão. Os resultados mostraram aumento na frequência de tumor epitelial em moscas tratadas 3,33 mL/g de refrigerantes à base de cola e de laranja, quando comparados ao controle negativo. Os refrigerantes diet cola e limão não provocaram aumento na frequência de tumor epitelial em D. melanogaster. Em conclusão, nessas condições experimentais, os refrigerantes à base de cola e laranja mostraram potencial carcinogênico em células somáticas de D. melanogaster na concentração de 3,33 mL/g.