Toxicity and genotoxicity induced by abacavir antiretroviral medication alone or in combination with zidovudine and/or lamivudine in Drosophila melanogaster.

Abacavir (ABC), zidovudine (AZT), and lamivudine (3TC) are nucleoside analog reverse transcriptase inhibitors (NRTIs) widely used as combination-based antiretroviral therapy against human immunodeficiency virus. Despite effective viral suppression using NRTI combinations, genotoxic potential of NRTIs can be increased when administered in combination. This study investigated the toxic and genotoxic potential of ABC when administered alone or in combination with AZT and/or 3TC using the somatic mutation and recombination test in Drosophila melanogaster. This test simultaneously evaluated two events related to carcinogenic potential: mutation and somatic recombination. The results indicated that ABC was responsible for toxicity when administered alone or in combination with AZT and/or 3TC. In addition, all treatment combinations increased frequencies of mutation and somatic recombination. The combination of AZT/3TC showed the lowest genotoxic activity compared to all combinations with ABC. Therefore, our results indicated that ABC was responsible for a significant portion of genotoxic activity of these combinations. Somatic recombination was the main genetic event observed, ranging from 83.7% to 97.7%.

Inhibitory effects of water extract of propolis on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster.

Propolis is a substance produced by honeybees (Apis mellifera L.). Its components are strong antioxidants and free radical scavengers. The aim of this study was to evaluate the protective effects of a water extract of Brazilian green propolis (WEP) combined with the antitumor agent doxorubicin (DXR) on Drosophila melanogaster wing cells through the somatic mutation and recombination test (SMART). Two different crosses were used: The standard (ST) cross and the high bioactivation (HB) cross. The HB cross is characterized by a constitutively enhanced level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Larvae obtained from these two crosses were chronically treated with different concentrations of WEP (12.5,25.0 and 50.0 mg/mL) alone or combined with DXR (0.125 mg/mL). The results obtained with the two different crosses were rather similar. Neither toxicity nor genotoxicity were observed in WEP treated series. Simultaneous treatment with different concentrations of WEP and DXR led to a reduction in the frequency of recombination compared to the treatment with DXR alone. This anti-recombinogenic effect was proportional to the concentrations applied, indicating a dose-response correlation and can be attributed to the powerful scavenger ability of WEP.

Body-composition changes with diet and exercise in obese women: a comparison of estimates from clinical methods and a 4-component model.

BACKGROUND: Most methods available to clinicians for estimating body-composition changes have been validated against estimates from densitometry, based on a 2-component (fat mass and fat-free mass) model. OBJECTIVE: Estimates of changes in percentage body fat (%BF) from dual-energy X-ray absorptiometry (DXA), skinfold thicknesses (SFTs), bioelectrical impedance analysis (BIA), and body mass index (BMI; in kg/m2) were compared with estimates from a 4-component (fat, water, mineral, and protein) model (%BFd,w,m), a more accurate method. DESIGN: Determinations of body density from hydrostatic weighing, body water from deuterium dilution, bone mineral and %BF from whole-body DXA, resistance from BIA, and anthropometric measures were made in 27 obese women (BMI: 31.1 +/- 4.9) assigned to 1 of 3 groups: control (C; n = 9), diet only (DO; n = 9), or diet plus aerobic exercise (DE; n = 9). RESULTS: After the 16-wk intervention, changes in body mass (BM) averaged 0.5 +/- 2.0, -7.2 +/- 7.4, and -4.0 +/- 3.3 kg and changes in %BFd,w,m averaged 2.1 +/- 1.0%, -1.2 +/- 1.4%, and -2.4 +/- 1.6% in the C, DO, and DE groups, respectively. Compared with changes in %BFd,w,m, the errors (SD of bias) for estimates of changes in %BF by DXA, BIA, SFTs, and BMI were similar (range: +/-2.0-2.4% of BM). BIA, SFTs, and BMI provided unbiased estimates of decreases in %BFd,w,m, but DXA overestimated decreases in %BF in the DO and DE groups. CONCLUSIONS: DXA, BIA, SFTs, and BMI are comparably accurate for evaluating body-composition changes induced by diet and exercise interventions; however, small changes in %BF may not be accurately detected by these clinical methods.

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.

Effects of diet and exercise on the density and composition of the fat-free mass in obese women.

PURPOSE: The purpose of this study was to determine whether the density (D(FFM)) and composition of the fat-free mass (FFM) and the accuracy of estimates of body composition from body density (%Fat(d)) are affected by diet and exercise. METHODS: Twenty-nine obese women (body mass index (BMI) = 25.0-43.7 kg x m(-2) and %Fat(d) = 35.7-47.1%) were assigned to one of three groups: diet only (DO, N = 9); diet and aerobic exercise (DE, N = 9); or control (C, N = 11). Measures of body density by hydrostatic weighing, body water by deuterium dilution, and bone mineral by whole-body dual-energy x-ray absorptiometry, and estimates of body composition from body density and from a four-component model were obtained before and after a 16-wk diet and exercise intervention. RESULTS: Mean (+/- SD) changes in body mass were -7.2 +/- 7.4, -3.9 +/- 3.3, and +1.2 +/- 2.8 kg for the DO, DE, and C, respectively. The density and composition of the FFM did not change significantly (P > 0.05) in any of the groups. Individual changes in D(FFM) (-0.011 to +0.011 g x mL(-1)), and differences between changes in %Fat estimated using a four-component model and %Fat(d) (-2.1 to +2.7% body mass) were not related to changes in body mass (r = -0.08). Individual changes in D(FFM) were most strongly related to changes in water fraction (r = -0.95) and protein fraction (r = +0.88), and were unrelated to changes in the mineral fraction (r = +0.04) of the FFM. CONCLUSIONS: We conclude that in obese women, the density and composition of the FFM are unaltered and densitometry correctly assesses group mean changes in body composition with moderate weight loss induced by diet or diet and aerobic exercise. However, individual deviations in D(FFM) from the assumed value of 1.1 g x mL(-1) are substantial, and a multi-component model in which body water is measured is needed to accurately assess individual body composition changes resulting from diet and exercise.

The effect of the dibenzylbutyrolactolic lignan (-)-cubebin on doxorubicin mutagenicity and recombinogenicity in wing somatic cells of Drosophila melanogaster.

The dibenzylbutyrolactolic lignan (-)-cubebin was isolated from dry seeds of Piper cubeba L. (Piperaceae). (-)-Cubebin possesses anti-inflammatory, analgesic and antimicrobial activities. Doxorubicin (DXR) is a topoisomerase-interactive agent that may induce single- and double-strand breaks, intercalate into the DNA and generate oxygen free radicals. Here, we examine the mutagenicity and recombinogenicity of different concentrations of (-)-cubebin alone or in combination with DXR using standard (ST) and high bioactivation (HB) crosses of the wing Somatic Mutation And Recombination Test in Drosophila melanogaster. The results from both crosses were rather similar. (-)-Cubebin alone did not induce mutation or recombination. At lower concentrations, (-)-cubebin statistically reduced the frequencies of DXR-induced mutant spots. At higher concentrations, however, (-)-cubebin was found to potentiate the effects of DXR, leading to either an increase in the production of mutant spots or a reduction, due to toxicity. These results suggest that depending on the concentration, (-)-cubebin may interact with the enzymatic system that catalyzes the metabolic detoxification of DXR, inhibiting the activity of mitochondrial complex I and thereby scavenging free radicals. Recombination was found to be the major effect of the treatments with DXR alone. The combined treatments reduced DXR mutagenicity but did not affect DXR recombinogenicity.

Recombinagenic activity of four compounds in the standard and high bioactivation crosses of Drosophila melanogaster in the wing spot test.

The wing somatic mutation and recombination test (SMART) using Drosophila melanogaster was employed to determine the recombinagenic and mutagenic activity of four chemicals in an in vivo eukaryotic system. Two different crosses involving the wing cell markers mwh and flr(3) were used: the standard cross and a high bioactivation cross. The high bioactivation cross is characterized by a high constitutive level of cytochromes P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Three-day-old larvae derived from both crosses were treated chronically with the oxidizing agent potassium chromate and with the three procarcinogens cyclophosphamide, p-dimethylaminoazobenzene and 9,10-dimethylanthracene. From both crosses two types of progeny were obtained: marker-heterozygous and balancer-heterozygous. The wings of both genotypes were analysed for the occurrence of single and twin spots expressing the mwh and/or flr(3) mutant phenotypes. In the marker-heterozygous genotype the spots can be due either to mitotic recombination or to mutation. In contrast, in the balancer-heterozygous genotype only mutational events lead to spot formation, all recombination events being eliminated. The oxidizing agent potassium chromate was equally and highly genotoxic in both crosses. Surprisingly, the promutagen cyclophosphamide also showed equal genotoxicity in both crosses, whereas p-dimethylaminoazobenzene was negative in the standard cross, but clearly genotoxic in the high bioactivation cross. 9,10-Dimethylanthracene showed a rather weak genotoxicity in the high bioactivation cross. Analyses of the dose-response relationships for mwh clones recorded in the two wing genotypes demonstrated that all four compounds are recombinagenic. The fraction of all genotoxic events which are due to mitotic recombination ranged from 83% (9,10-dimethylanthracene) to 99% (p-dimethylaminoazobenzene). These results demonstrate that the wing spot test in Drosophila is most suited to the detection of recombinagenic activity of genotoxic chemicals.