Modulating effect of losartan potassium on the mutagenicity and recombinogenicity of doxorubicin in somatic cells of Drosophila melanogaster.

Losartan potassium is an antihypertensive drug in the angiotensin II receptor antagonist (ARA) class. Some studies claim that, in addition to regulating blood pressure, this class of drug has anticancer properties. The objective of this study was to evaluate the genotoxic and antigenotoxic potential of losartan potassium using the SMART (Somatic Mutation and Recombination Test) assay on the somatic cells of Drosophila melanogaster, as well as the possible modulating effects of this drug, when associated with doxorubicin (DXR). Third instar larvae, descendents of standard and high bioactivation (ST and HB) crosses, were chronically treated with different concentrations of losartan potassium (0.25; 0.5; 1; 2; and 4 mM) alone or in association (co-treatment) with doxorubicin (DXR 0.125 mg/mL). The results showed an absence of a mutagenic effect of losartan potassium. In the co-treatment of losartan with DXR, the results showed that losartan is capable of reducing the number of mutant spots induced by DXR without altering the recombinogenic effect of the chemotherapeutic agent. Antiproliferative action appears to be the main mechanism involved in reducing the frequency of mutant spots and consequent modulation of alterations induced by DXR, although this parameter has not been directly assessed in this study.

Modulating effect of simvastatin on the DNA damage induced by doxorubicin in somatic cells of Drosophila melanogaster.

Simvastatin is an antilipemic drug that promotes inhibition of HMG-CoA reductase. Simvastatin can also inhibit the formation of other products, such as isoprenoids, conferring additional benefits to this drug, which include antiproliferative, anti-invasive and pro-apoptotic effects. This study was carried out with the aim of evaluating the mutagenic/recombinogenic effect of simvastatin as well as the possible modulatory effects of this statin on the DNA damage induced by doxorubicin (DXR). This analysis was performed using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. To study these effects, larvae descendants of both crosses (ST and HB) were chronically treated with five concentrations of simvastatin, separately and in association with DXR. The results revealed no mutagenic/recombinogenic effect of simvastatin for any of the concentrations tested. A modulating effect of simvastatin was also observed on DNA damage induced by DXR. The reduction of total mutant frequency was observed for spots from descendants of both crosses, but the inhibition was more effective in descendants from the standard cross (ST). It is believed that this modulating effect is mainly associated with the antioxidant activity of this class of drugs, although this parameter has not been directly assessed in this study.

Modulating effect of synthetic statins against damage induced by doxorubicin in somatic cells of Drosophila melanogaster.

The competitive inhibitors of HMG-CoA reductase, popularly known as statins, exert pleiotropic effects, which result from the ability of statins to inhibit the synthesis of isoprenoids, which are fundamental for the functioning of proteins responsible for intracellular signaling. Some recent studies suggest an important role associated with the use of antineoplastic atorvastatin and rosuvastatin, the statins most widely used today. In this study, the Drosophila wing spot test was used to evaluate possible protective effects of atorvastatin and rosuvastatin against damage induced by DXR. Larvae were chronically treated with negative control (ethanol 5%), positive control (DXR 0.125 mg/mL) and five different concentrations of atorvastatin and rosuvastatin. The results demonstrated absence of a mutagenic effect for the two statins tested. The analysis of the descendants co-treated with DXR and atorvastatin/rosuvastatin revealed a modulatory effect of these statins on damage induced by DXR. This effect was verified in all concentrations tested in the descendants of the ST and HB crosses treated with rosuvastatin, and only in descendants of the HB cross treated with atorvastatin. Induction of apoptosis and antioxidant activity appear to be the main mechanisms involved in reducing the frequency of mutant spots and consequent modulation of the damage induced by DXR.

Lack of mutagenic effect by multi-walled functionalized carbon nanotubes in the somatic cells of Drosophila melanogaster.

Carbon nanotubes (CNTs) are formed by rolling up a single graphite sheet into a tube. Among the different types of CNTs, the multi-walled carbon nanotubes (MWCNTs) comprise a set of concentric nanotubes with perfect structures. Several uses for MWCNTs have been suggested to be included in biological applications such as manufacturing of biosensors, carriers of drugs. However, before these materials can be put on the market, it is necessary to know their genotoxic effects. Thus, this study aims to evaluate the mutagenicity of multi-walled carbon nanotubes (MWCNTs) functionalized in somatic cells of Drosophila melanogaster, using the somatic mutation and recombination test (SMART). This assay detects the loss of heterozygosity of marker genes expressed phenotypically on the wings of the fly. Larvae of three days were used, resulting from ST cross, with basal levels of the cytochrome P450 and larvae of high metabolic bioactivity capacity (HB cross). They were treated with different concentrations of MWCNTs functionalized. The MH descendants, analyzed in both ST and HB crosses, had no significant effects on the frequency of mutant. Based on the results and on the experimental conditions mentioned in this study, it was concluded that MWCNTs were not mutagenic in D. melanogaster.

Assessment of the mutagenic, recombinagenic and carcinogenic potential of orlistat in somatic cells of Drosophila melanogaster.

In this study the mutagenic, recombinagenic, carcinogenic and anticarcinogenic potential of orlistat was assessed using the somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts). The experiments were conducted on Drosophila melanogaster. In the assessment using SMART, larvae, descendants from the standard (ST) cross and the high bioactivation (HB) cross, were treated chronically with three orlistat concentrations. The results revealed a recombinagenic effect, associated with orlistat, in the descendants of the HB cross, at all three levels of concentration. Homologous recombination can function as a determinant at different stages of carcinogenesis. For verification, larvae from the wts test, descendants of the wts/TM3 virgin female and mwh/mwh male cross, were treated with the same three orlistat concentrations separately and in association with mitomicin C (0.1mM). The results did not, however, provide evidence that orlistat has carcinogenic potential nor was it associated with the reduction of tumors induced by mitomicin C in D. melanogaster.

Lapachol as an epithelial tumor inhibitor agent in Drosophila melanogaster heterozygote for tumor suppressor gene wts.

The search for new and effective antitumor agents with fewer cytotoxic side effects on normal tissue has increasingly become important. Lapachol, a natural organic compound isolated from the lapacho tree (Tabebuia avellandedae), is chemically identified as belonging to the naphthoquinone group and is known for its anti-inflammatory, analgesic and antibiotic properties, although there are questions about its effectiveness for treating neoplasic cells. We evaluated the antitumoral effects of lapachol by testing for clones of epithelial tumors in Drosophila melanogaster. Seventy-two-hour old larvae bred from wts/TM3, Sb(1) females and mwh/mwh males, were treated with different concentrations of lapachol (20, 40 and 60 µg/mL). Lapachol alone did not significantly increase the number of epithelial tumors. However, lapachol did significantly reduce the number of tumors provoked by doxorubicin.

Protective effects of beta-carotene against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster.

beta-carotene (BC), pro-vitamin A, is an efficient antioxidant, effective in the neutralization of oxygen reactive species, which cause serious damage to DNA. Various studies have been conducted on the effectiveness of BC for chemoprevention of cancer and heart disease. Doxorubicin is a chemotherapeutic agent used for cancer treatment that generates free radicals. We examined the effects of BC (1, 2 and 4 mg/mL) on the genotoxicity of doxorubicin (0.125 mg/mL), using the wing spot test in Drosophila melanogaster (somatic mutation and recombination test). The BC alone had no significant effect on the frequency of mutant spots. However, it significantly reduced the number of spots caused by doxorubicin. We concluded that BC is not genotoxic and that it exerts protective effects against the genotoxic action of the chemotherapeutic free-radical generator doxorubicin.

Recombinogenic effects of the aqueous extract of pulp from pequi fruit (Caryocar brasiliense) on somatic cells of Drosophila melanogaster.

Caryocar brasiliense Camb. is a tree popularly known in Central Brazil as pequi. Its fruit contains carotenes, retinols, vitamin C, and polyphenols. These compounds possess antioxidant properties preventing excessive free radical formation and modulating the genotoxicity of physical and chemical agents in the body. However, at high concentrations these compounds can have recombinogenic and mutagenic effects, because they can act as pro-oxidants. We examined the genotoxic effects of aqueous extracts of pequi pulp on wing spots of Drosophila melanogaster using the somatic mutation and recombination test (SMART). SMART was applied to a standard cross and to a high bioactivation cross. Two types of descendants were obtained from these crosses: marked-heterozygous (mwh + / + flr3) and balancer-heterozygous (mwh + / + TM3, Bds). Seventy-two-hour larvae from both crosses were treated with pequi pulp extract at 1, 5 and 10%. The extract increased significantly the frequency of mutant spots when compared with the negative control. Recombinogenic effects were also observed in the mwh/TM3 descendants.

Efeito protetor do chá de cogumelo do sol (Agaricus blazei Murill) contra a ação genetóxica do uretano em células somáticas de Drosophila melanogaster / Protective effect of the tea of sun mushroom (Agaricus blazei Murill) against genetoxic action of urethane on somatic cells of Drosophila to melanogaster

O Agaricus blazei vem sendo utilizado popularmente no tratamento de uma série de doenças: diabetes, redução do colesterol, stress físico e até mesmo câncer. Sua possível ação tumoricida está associada à ativação de células Natural Killer. Para avaliar os possíveis efeitos protetores do chá de A. blazei (62,5 g.L-1) contra a ação genotóxica do uretano (10mM), utilizou-se o Teste para Detecção de Mutação e Recombinação Somática (Somatic Mutation And Recombination Test-SMAT). Foram utilizadas larvas de 72 ± 4h, resultantes dos cruzamentos padrão e alta bioativação metabólica. Os resultados obtidos demonstraram que não houve aumento, estatisticamente significativo, nas freqüências de manchas mutantes, em larvas expostas ao chá de A. blazei. Quando A. blazei foi associado ao uretano, foi observada uma redução estatisticamente significativa nas freqüências das manchas mutantes. Os resultados sugerem que o A. blazei não é genotóxico e exerce um efeito protetor contra a ação genotóxica do uretano.

Detection of micronuclei in peripheral erythrocytes of Cyprinus carpio exposed to metallic mercury.

Cyprinus carpio fish (carp), exposed to elemental or metallic mercury (Hg0) at concentrations of 2.0, 20.0, and 200.0 mg per liter of water, were kept in concrete tanks for 159 days. Ten fish were used for each concentration level. Thirteen samples of peripheral blood were collected from each animal through gill puncture, 12 during the first 90 days of the experiment, and the last one at the end of the experiment. The micronucleus test (MNT) was designed to study dose and time yield effects of mercury after indirect exposure in vivo. The results indicated that for a concentration of 2.0 mg Hg0/l, there was no significant increase in frequency of micronuclei (MN), but at higher concentrations (20.0 and 200.0 mg Hg0/l) there was a significant increase in MN frequencies. This effect was higher after 31 days of exposure, followed by slight stabilization and gradual decrease.