Inhibitor of poly(ADP-ribose)transferase potentiates the recombinogenic but not the mutagenic action of alkylating agents in somatic cells in vivo in Drosophila melanogaster

Mutagenesis ◽  
1990 ◽  
Vol 5 (5) ◽  
pp. 511-514 ◽  
Author(s):  
Jan Magnusson ◽  
Claes Ramel
Keyword(s):  
Drosophila Melanogaster ◽  
Alkylating Agents ◽  
Somatic Cells ◽  
Mutagenic Action

DISCLOSING THE TRUE NATURE OF HESPERETIN’S ANTIGENOTOXICITY „IN VIVO“ WITHIN THE „DROSOPHILA MELANOGASTER“ SOMATIC CELLS THROUGH THE EXTENSIVE GENOTOXICAL AND STRUCTURE-BASED STUDIES

2021 ◽  
Author(s):  
Sanja Matić ◽  
◽  
Snežana Stanić ◽  
Nevena Tomašević ◽  
Rino Ragno ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Alkylating Agents ◽  
Somatic Cells ◽  
Competitive Inhibitor ◽  
Metabolic Energy ◽  
True Nature ◽  
Catalytic Inhibitor ◽  
Hydrolysis Of ◽  
Cleavage Domain

Previously unreported genotoxic and antigenotoxic potentials of hesperetin (Hes) were revealed by treating the Drosophila melanogaster (dm) whose DNA has been altered by means of O6-ethylguanine (dmGO6-Et) and O4-ethylthymine (dmTO4-Et) lesions appearance, caused by ethyl methanesulfonate (EMS), a proven alkylating agent and mutagen. Therefore, Hes potencies were determined by means of the comet assay on somatic cells level, where compound exerted no genotoxic effects but acted genotoxically as a Topoisomerase IIα (dmTopIIα) catalytic inhibitor by invading the Binding and Cleavage Domain and stabilizing the noncovalent dmTopIIα-plasmid DNA (dmPDNA) complex, as verified by the kinetoplast DNA (dmK-DNA) decatenation assays. Hes’s structure-based alignment caused compound’s A and C rings to occupy the area normally invaded by EMS, thus making a spatial barrier for the dmGO6-Et or dmTO4-Et lesions formation: the A ring C7-OH group formed hydrogen bonds (HBs) with either dmGO6 (dHB = 2.576 Å) or guanine’s N7 nitrogen (dmGN7, dHB = 2.737 Å), whereas the A ring C5-OH group formed an HB with dmTO4 (dHB = 3.548 Å). Furthermore, Hes likewise acted as a mixed-type competitive inhibitor of dmATPase, as verified by the catalytic, FRET, and structure-based studies where it affected the dmATPase dimerization and the hydrolysis of ATP, denying the metabolic energy for the catenation of ethylated G-dmDNA segment, the formation of dmTO4-Et-G-dmDNA phosphotyrosine intermediate (dmTO4-Et-G- dmDNA-PTyr785I), and the passage of ethylated T-dmDNA segment through the temporarily broken dmTO4-Et-G-dmDNA-PTyr785I, processes seen as comets. Conclusively, Hes may be used in anticancer therapy controlling the effects of alkylating agents.

DNA-damaging potency and genotoxicity of aflation M1 in somatic cells in vivo of Drosophila melanogaster

Mutagenesis ◽  
1995 ◽  
Vol 10 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Toshikazu Shibahara ◽  
H.Iyehara Ogawa ◽  
Haruko Ryo ◽  
Kazuo Fujikawa
Keyword(s):  
Drosophila Melanogaster ◽  
Somatic Cells

scholarly journals Genotoxicity of Copper and Nickel Nanoparticles in Somatic Cells of Drosophila melanogaster

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Erico R. Carmona ◽  
Alba García-Rodríguez ◽  
Ricard Marcos
Keyword(s):  
Drosophila Melanogaster ◽  
Laser Doppler Velocimetry ◽  
Antimicrobial Agents ◽  
Nickel Nanoparticles ◽  
Somatic Cells ◽  
Industrial Applications ◽  
Electronic Microscopy ◽  
Genotoxic Effects

Copper and nickel nanoparticles (Cu-NPs and Ni-NPs, respectively) are used in a variety of industrial applications, such as semiconductors, catalysts, sensors, and antimicrobial agents. Although studies on its potential genotoxicity already exist, few of them report in vivo data. In the present study we have used the wing-spot assay in Drosophila melanogaster to determine the genotoxic activity of Cu-NPs and Ni-NPs, and these data have been compared with those obtained with their microparticle forms (MPs). Additionally, a complete physical characterization of NPs using transmission electronic microscopy (TEM), dynamic light scattering (DLS), and laser Doppler velocimetry (LDV) techniques was also performed. Results obtained with Cu-NPs and Cu-MPs indicate that both failed to induce an increase in the frequency of mutant spots formation in the wings of the adults, suggesting a lack of genotoxicity in somatic cells of D. melanogaster. However, when Ni-NPs and Ni-MPs were evaluated, a significant increase of small single spots and total mutant spots was observed only for Ni-NPs (P<0.05) at the highest dose assessed. Thus, the genotoxicity of Ni-NPs seem to be related to their nanoscale size, because no genotoxic effects have been reported with their microparticles and ions. This study is the first assessing the in vivo genotoxic potential of Cu-NPs and Ni-NPs in the Drosophila model.

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