Kenya Silva Cunha

Co-mutagenic effect of tannic acid on ring-X chromosome loss induced by mitomycin C in sperm cells of Drosophila melanogaster

To investigate the effects of tannic acid (TA) on ring-X chromosome loss, Drosophila melanogaster females exposed to different TA concentrations were crossed with untreated, methyl methanesulfonate (MMS)- or mitomycin C (MMC)-treated males which carried a ring-X chromosome. Progeny were analyzed for loss of the ring-X. The results of this in vivo study showed that TA had no suppressing effect on chromosome loss occurring spontaneously or after induction by MMS in mature spermatozoa. In contrast, TA caused a significant increase in the frequency of MMC-induced ring-X loss. The increase caused by this co-mutagenic effect reached values of 34, 33 and 40% at TA concentrations of 10, 25 and 50 mM, respectively. These increments may reflect the action of TA on a uvrABC-type enzyme which, by increasing the double-strand breaks (DSBs), somehow interferes with the post-replicational repair responsible for the final DSB correction.

Antimutagenic and antirecombinagenic activities of noni fruit juice in somatic cells of Drosophila melanogaster

Noni, a Hawaiian name for the fruit of Morinda citrifolia L., is a traditional medicinal plant from Polynesia widely used for the treatment of many diseases including arthritis, diabetes, asthma, hypertension and cancer. Here, a commercial noni juice (TNJ) was evaluated for its protective activities against the lesions induced by mitomycin C (MMC) and doxorrubicin (DXR) using the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for two genetic markers (mwh and flr3 ), were co-treated with TNJ plus MMC or DXR. We have observed a reduction in genotoxic effects of MMC and DXR caused by the juice. TNJ provoked a marked decrease in all kinds of MMC- and DXR-induced mutant spots, mainly due to its antirecombinagenic activity. The TNJ protective effects were concentration-dependent, indicating a dose-response correlation, that can be attributed to a powerful antioxidant and/or free radical scavenger ability of TNJ.

Assessment of complex genomic alterations induced by AZT, 3TC, and the combination AZT +3TC

Abstract Highly active antiretroviral therapy (HAART) regimens are based on the use of nucleoside reverse transcriptase inhibitors (NRTIs), which are the main drugs used by patients infected with the human immunodeficiency virus (HIV). The use of NRTIs combinations has afforded clear clinical benefits to patients undergoing HAART. However, the combination of two NRTIs may increase the risk of genomic instability in comparison with the drugs administered individually. We analyzed the ability of zidovudine (AZT) and lamivudine (3TC), and the combination AZT +3TC to induce complex genomic alterations using the cytokinesis-block micronucleus (CBMN) assay in Chinese hamster ovary (CHO)-K1 cells. The 24-h cell treatment with individual NRTIs showed that AZT increased micronucleus frequencies and nucleoplasmic bridges (NPBs). No significant differences were observed for any parameters investigated after exposure of CHO-K1 cells to 3TC. The combination AZT +3TC significantly increased micronucleus frequencies. Analysis of interaction between these drugs suggested that antagonism occurs in all AZT +3TC concentrations. These results highlight the importance to investigate the genotoxic profile of NRTIs to develop safer intervention strategies in antiretroviral treatment protocols.