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

• Published in: Food and chemical toxicology Vol. 143; p. 111549
• Main Authors: Vasconcelos, Mirley Alves, Orsolin, Priscila Capelari, Oliveira, Victor Constante, Lima, Paula Marynella Alves Pereira, Naves, Maria Paula Carvalho, de Morais, Cássio Resende, Nicolau-Júnior, Nilson, Bonetti, Ana Maria, Spanó, Mário Antônio
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2020
• Subjects: Animals; Antibiotics, Antineoplastic - toxicity; Calcium-Regulating Hormones and Agents - pharmacology; Carcinogenesis - drug effects; Cholecalciferol; Cholecalciferol - pharmacology; Docking molecular; Doxorubicin - toxicity; Drosophila melanogaster - drug effects; Drosophila melanogaster - genetics; Epithelial tumor test; Female; Male; Models, Molecular; Molecular dynamics; Molecular Dynamics Simulation; Molecular Structure; Mutation - drug effects; Protein Conformation; Receptors, Calcitriol - chemistry; Receptors, Calcitriol - metabolism; Recombination, Genetic; Smart; Somatic mutation and recombination test; Molecular dynamics; Epithelial tumor test; Docking molecular; Smart; Somatic mutation and recombination test; Cholecalciferol
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2020.111549

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.
•VD3 was not toxic, mutagenic neither carcinogenic to Drosophila melanogaster.•VD3 has modulatory effects on the mutagenicity and carcinogenicity induced by DXR in Drosophila.•VD3 revealed a modulatory effect without altering the recombinogenic activity of DXR.•VD3 showed satisfactory interactions with the Ecdysone Receptor (EcR).