Somatic Mutation And Recombination Test Assay Research Articles

Antigenotoxic and Lifespan-Promoting Effects of Flavoured Kombuchas on Drosophila melanogaster

Research background. Kombucha is a fermented beverage with several health benefits; however, to improve its antioxidant activity, new raw materials consisting of hop, madimak, and hawthorn were included in the present study. Experimental approach. The Drosophila Somatic Mutation and Recombination Test (SMART) was used to evaluate the antigenotoxic potential of black tea kombucha and three-flavoured kombuchas (hop, madimak, and hawthorn) against H2O2- and K2Cr2O7-induced genotoxicity. Furthermore, a lifespan assay was performed to assess the effects of kombuchas on Drosophila longevity. Results and conclusions. According to the results obtained from the SMART assay, hop-flavoured kombucha attenuated genotoxicity induced by H2O2, and madimak-flavoured kombucha reduced genotoxicity induced by H2O2 and K2Cr2O7. Black tea kombucha and hop-flavoured kombucha prolonged the lifespan of Drosophila after H2O2 and K2Cr2O7 exposure. Novelty and scientific contribution. Hop-flavoured kombucha is a promising antioxidant that protects the genome and extends the lifespan of Drosophila. This study sheds light on novel beverages that can combat aging and protect against genotoxicity.

Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing-A Review.

Genomic instability, one of cancer’s hallmarks, is induced by genotoxins from endogenous and exogenous sources, including reactive oxygen species (ROS), diet, and environmental pollutants. A sensitive in vivo genotoxicity test is required for the identification of human hazards to reduce the potential health risk. The somatic mutation and recombination test (SMART) or wing spot test is a genotoxicity assay involving Drosophila melanogaster (fruit fly) as a classical, alternative human model. This review describes the principle of the SMART assay in conjunction with its advantages and disadvantages and discusses applications of the assay covering all segments of health-related industries, including food, dietary supplements, drug industries, pesticides, and herbicides, as well as nanoparticles. Chemopreventive strategies are outlined as a global health trend for the anti-genotoxicity of interesting herbal extract compounds determined by SMART assay. The successful application of Drosophila for high-throughput screening of mutagens is also discussed as a future perspective.

Synthesis, Characterization, and Optimization of Green Silver Nanoparticles Using Neopestalotiopsis clavispora and Evaluation of Its Antibacterial, Antibiofilm, and Genotoxic Effects

Abstract Silver nanoparticles (AgNPs) have been used in a variety of biomedical applications in the last two decades, including antimicrobial, anti-inflammatory, and anticancer treatments. The present study highlights the extracellular synthesis of silver nanoparticles AgNPs using Neopestalotiopsis clavispora MH244410.1 and its antibacterial, antibiofilm, and genotoxic properties. Locally isolated N. clavispora MH244410.1 was identified by Internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA. Optimization of synthesized AgNPs was performed by using various parameters (pH (2, 4, 7, 9 and 12), temperature (25, 35 and 45 °C), and substrate concentration (0.05, 0.1, 0.15, 0.2 and 0.25 mM)). After 72 hours of incubation in dark conditions, the best condition for the biosynthesis of AgNPs was determined as 0.25 mM metal concentration at pH 12 and 35 °C. Fungal synthesized AgNPs were characterized via spectroscopic and microscopic techniques such as Fouirer Transform Infrared Spectrophotometer (FTIR), UV-Visible Spectroscopy, and Transmission Electron Microscopy (TEM). The average size of the AgNPs was determined less than 60 nm using the TEM and Zetasizer measurement system (measured in purity water suspension). The characteristic peak of AgNPs was observed at ~414 nm from UV-Vis results. Antibacterial and genotoxic activity of synthesized AgNPs (0.1, 1, and 10 ppm) were also determined by using the agar well diffusion method and in vivo Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. AgNPs exhibited potential antimicrobial activity against all the tested bacteria (Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa) except Escherichia coli in a dose-dependent manner. AgNPs did not induce genotoxicity in the Drosophila SMART assay. 79.33, 65.47, and 41.95% inhibition of biofilms formed by P. aeruginosa were observed at 10, 1, and 0.1 ppm of AgNPs, respectively. The overall results indicate that N. clavispora MH244410.1 is a good candidate for novel applications in biomedical research.

EVALUATION OF GENOTOXICITY OF THREE FOOD PRESERVATIVES IN DROSOPHILA MELANOGASTER USING SMART AND COMET ASSAYS

The continuously growing food and beverage industry relies on food additives as a main component in their products. Such increased reliance on processed food, lead to neglectance of the harmful effects of the food additives on human health; among these are hypersensitivity, allergic reactions, genotoxicity, mutagenicity and more. This study investigates genotoxic effects of three food preservatives commonly consumed in daily meals; sodium sulphite, boric acid, and benzoic acid using the somatic mutation and recombination test (SMART) and comet assay in Drosophila melanogaster system. All of the tested compounds showed significantly high levels of tumor induction and frequency compared to a negative control in SMART assay. They also showed high amount of DNA damage in the comet assay indicating their high potential of being genotoxic materials.

Assessment of the Mutagenicity of Propolis Compounds from the Brazilian Cerrado Biome in Somatic Cells of Drosophila melanogaster

Few information on the biological properties of the chemical constituents of propolis produced by Apis mellifera from the Cerrado of Midwest Brazil has hitherto been reported. In the present work, the mutagenic properties of five compounds isolated from a sample of brown propolis from the aforesaid biome, namely, caffeic ( 1 ), p-coumaric ( 2 ), dihydro-p-coumaric ( 3 ), and acetylisocupressic ( 4 ) acids, and aromadendrin ( 5 ) have been assessed by performing the somatic mutation and recombination test (SMART) on wing cells of Drosophila melanogaster, using standard (ST) and high bioactivation (HB) crosses. This is the first report of assessment of the mutagenic potential of 2 - 4 , and using the SMART assay for 5 . No mutagenicity was induced by 1 - 3 and 5 in the descendants from the ST and HB crosses at all evaluated concentrations. However, 1 and 2 , unlike 3 , were shown to be toxic to descendants of both ST and HB crosses. A structure-activity relationship established among 1 - 3 revealed that a C-7/C-8 unsaturation is responsible for the toxic effect of 2 compared to 3 , while an additional ortho-dihydroxy substitution at C-3 and C-4 confers to 1 the highest toxicity to D. melanogaster flies. Diterpene 4 proved mutagenic only after P450 activation, suggesting that it may act as a promutagen compound. DOI: http://dx.doi.org/10.17807/orbital.v11i5.1418

Ameliorative effects of melatonin against nano and ionic cobalt induced genotoxicity in two in vivo Drosophila assays

The aim of this study is to evaluate the ameliorative effect of melatonin (MEL) against induced genotoxicity by cobalt (II) chloride (CoCl2) and cobalt nanoparticles (CoNPs) (50 nm). Genotoxicity of CoCl2 and CoNPs were investigated using single cell gel electrophoresis (COMET) in Drosophila melanogaster hemocytes, which are blood cells of the Drosophila, and the somatic mutation and recombination test (SMART) was used to investigate mutant effects on the Drosophila wings. Three concentrations (0.1, 1, and 10 mM) of CoNPs and CoCl2 were applied to demonstrate their genotoxic potential. Both CoNPs and CoCl2 have mutagenic potential for the three concentrations tested in the COMET assay; however, only the 10 mM concentration of the ionic form and two high concentrations (1 and 10 mM) of CoNPs induced genotoxicity in the Drosophila SMART assay. Three different concentrations of MEL (0.1, 0.5 and 2.5 mM) were used against cobalt at highest concentration (10 mM) of both CoCl2 and CoNPs in both the SMART and COMET assays. MEL ameliorated the genotoxicity induced by CoCl2 and CoNPs in vivo Drosophila COMET and SMART assays.

Assessment of Genotoxicity of Potassium Nitrate and Sodium Benzoate in Drosophila melanogaster Using Smart and Comet Assays

Modern food industry increasingly relies on food additives. The dramatic increase in the demand on preserved ready to eat food products making up to 75 percent of the diet of western society lead to neglectance of the harmful effects of the food additives on human health; among these are hypersensitivity, allergic reactions, genotoxicity, mutagenicity and more. This proposal investigates genotoxic effects of two commonly used food preservatives; sodium benzoate and potassium nitrate using the somatic mutation and recombination test (SMART) and comet assay. Two important end points of genotoxicity can be covered by in vivo assay systems; comet assay detects DNA damage, while the Drosophila transgenic animal model recognizes gene mutation and/or chromosomal aberrations. Both of the tested compounds showed significantly high levels of tumor induction and frequency compared to a negative control in SMART assay accompanied with a significant amount of DNA damage detected by the comet assay indicating their high potential of being genotoxic materials

Titanium dioxide nanoparticles: Toxicity and genotoxicity in Drosophila melanogaster (SMART eye-spot test and comet assay in neuroblasts)

Titanium dioxide nanoparticles (TiO2NP) are used in the food, drug, and cosmetics industries and evaluation of their human and environmental toxicity is required. We have tested the toxicity of TiO2NP (anatase) with respect to developmental effects and DNA damage in Drosophila melanogaster strain Ok, using the eye-spot Somatic Mutation and Recombination Test (SMART) and the comet assay (neuroblasts). For the survival assay, TiO2NP were supplied to adult flies for 72 h and no adverse effects were seen. TiO2NP were supplied chronically for the prolificacy, SMART, and comet assays. TiO2NP increased fly prolificacy. With regard to genotoxicity, an increase was observed in the eye-spot SMART assay at 8 μg/mL dose, but not in the neuroblast comet assay for DNA damage.

GENETIC EFFECT OF MIGRATORY COMPOUNDS FROM BOTTLED NATURAL DRINKING WATER STORED UNDER DIRECT SUNLIGHT

The drinking water is one of the important routes for human exposure to contaminants through releasing of antimony (Sb) and polymers from polyethylene terephthalate (PET) plastic. The aim of this study was to investigate the effect of sunlight on chemical compounds migration into PET-bottled water and studying the cytotoxicity of di-butyl phthalate (DBP) and di-octyl phthalate (DOP) by SMART in Drosophila melanogaster. Four random water bottle samples produced by various companies as: A (PET, clear, 0.6L), B (PET, clear, 1.5L), C (PET, blue, 1.5L) and D (polycarbonate PC, blue, 19L) for studying the effect of direct sunlight exposure on migration of antimony and phthalates. Experiment was carried out in the presence of sunlight (7 h daily) for 210 day. The migrated compounds profile (µg/L) that detected sample (A) before storage were only two compounds formaldehyde (FA) and acetaldehyde (AA) out of nine compounds. During storage under sunlight, four compounds (Sb), bis-phenol A (BPA), dimethyl phthalate (DMP) and diethyl phthalate (DEP) were increased till 30th day then did not affect till the end of storage. Other detected compounds were continuously progressed till the end of storage with different rates. The highest rate was appeared in case of FA, it was 222 fold followed by DOP compound (173 fold) as well as DBP (75.3 fold) and finally the AA compound with 17.9 fold. Regarding to another sample B, only 3 compounds (BPA, DMP and DBP) were not detected at zero time. The AA compound was detected with the highest concentration (0.9µg/L) and the lowest one was DOP (0.007µg/L). Only four compounds were detected before storage named Sb, DOP, FA and AA, the lowest level (0.006µg/L) was noticed in DOP, while the moderate level was recorded in FA (0.03µg/L) and Sb (0.08µg/L). Other detected compounds; i.e. DBP, DOP, AA and FA were consequently increased with higher levels. This study investigated genotoxic effects of (DBP) and (DOP) at 30µg/ml concentration using the somatic mutation and recombination test (SMART). The cytotoxicity of the tested phthalate compounds was also assessed at five different concentrations 0.5, 1, 5, 10 and 20µg/ml in two types of human cell lines; liver cancer (HepG2), colon cancer (HCT-116) using neutral red cytotoxicity assay. All of tested compounds significantly showed high levels of tumor induction and frequency compared to the negative control in SMART assay. It was also reduced the viability of the HepG2 cell lines cells using different concentrations and the highest cytotoxic effect. While, on HCT-116 showed no cytotoxic effect.

Carcinogenic and Cytotoxic Effect of Some Food Additives on Drosophila melanogaster and Human Cell Lines

Some food additives that are commonly used by humans were recently proved to be mutagenic. It is of significant importance to evaluate their genotoxic effects, since they are frequently consumed by humans in their daily meals. In this proposal, we investigated the effects of sodium sulphite, boric acid, and benzoic acid on human cell lines; liver cancer (HepG2), colon cancer (HCT-116), lung cancer (A-459), and normal lung (Wi38) and cells were evaluated using neutral red cytotoxicity assay and assessed using the somatic mutation and recombination test (SMART). These compounds at 100mM concentrations induced tumor induction and increased the frequency compared to a negative control in SMART assay. Also, they reduced the viability of the four examined cell lines cells using different concentrations (75, 150, 300 and 600µg/ml). Boric acid had the highest toxic effect while benzoic had the lowest on the examined cells. The toxicity effect of the tested food additives was higher on normal lung human cells than on lung cancer cells, therefore, these food additives may act as carcinogenic agents

Genotoxic evaluation of different sizes of iron oxide nanoparticles and ionic form by SMART, Allium and comet assay

In this study, the genotoxic potential of <50 nm, <100 nm iron oxide (Fe2O3) nanoparticles (IONPs) and ionic form were investigated using the wing somatic mutation and recombination test (SMART) and Allium and comet assays. In the SMART assay, different concentrations (1, 2, 5 and 10 mM) of NPs and ionic forms were fed to transheterozygous larvae of Drosophila melanogaster. No significant genotoxic effect was observed in <100 nm NPs and ionic form, while <50 nm IONPs showed genotoxicity at 1 and 10 mM concentrations. Allium cepa root meristems were exposed to five concentrations (0.001, 0.01, 0.1, 1 and 10 mM) of <50 nm and ionic forms for 4 h and three concentrations (2.5, 5 and 10 mM) for <100 nm of IONPs for 24 and 96 h. There was a statistically significant effect at 96 h at all concentrations of <100 nm IONPs. Similarly, <50 nm of IONPs and ionic forms also showed a statistically significant effect on mitotic index frequencies for all concentrations at 4 h. There was a dose-dependent increase in chromosomal abnormalities for IONPs and ionic form. Comet assay results showed time- and concentration-dependent increases in <100 nm NPs. There was a concentration-dependent increase in <50 nm NPs and ionic form ( p < 0.05). Consequently, the <50 nm of Fe2O3 was found toxic compared to 100 nm Fe2O3 and ionic form.

Assessment of the mutagenic, recombinogenic, and carcinogenic potential of amphotericin B in somatic cells of Drosophila melanogaster

Amphotericin B (AmB) is an antifungal antibiotic extracted from Streptomyces nodosus. Its fungicidal activity depends primarily on its binding to the sterol group that is present in fungal membranes. In view of the toxicity of this drug, the purpose of this study was to evaluate its mutagenic, carcinogenic, and recombinogenic activity, based on the wing somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts) applied to Drosophila melanogaster. Larvae were chronically treated with different concentrations of AmB (0.01, 0.02, and 0.04 mg/mL). The results revealed that AmB is a promutagen exhibiting increase in the number of spots on individuals from high bioactivation (HB) cross with a high level of cytochrome P450. The results also indicate that the main genotoxic event induced by AmB is recombinogenicity. Homologous recombination can act as a determinant at different stages of carcinogenesis. For verification of carcinogenic potential of this compound, larvae from the wts/mwh and wts/ORR, flr3 were treated with the same three AmB concentrations used in the SMART assay. The results did not provide evidence that AmB has carcinogenic potential in wts/mwh individuals. However, individuals from wts/ORR, flr3 developed tumors at the highest concentration tested.

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.

In vivo Genotoxicity of Four Synthetic Pyrethroids with Combinations of Piperonyl Butoxide (PBO) Using the Drosophila SMART Assay

In this study, the genotoxic effects of four synthetic pyrethroids (cypermethrin, cyphenothrin, deltamethrin, and permethrin) alone and their combinations with different rates of piperonyl butoxide (PBO) were studied using the wing somatic mutation and recombination test (SMART) of the Drosophila melanogaster. In the first stage, lethal concentration values (LC 25 or LC 50 ) of the synthetic pyrethroids and concentrations of PBO used for the synthetic pyrethroids were determined. Then, Drosophila larvae were exposed to lethal concentrations of synthetic pyrethroids and combinations with different rates of PBO (1:0.25, 1:0.5, 1:0.75, 1:1, and 1:2). According to the obtained results, alone and with the PBO of the mixtures of the four synthetic pyrethroids are not genotoxic when compared with the negative control. In addition, the PBO when used alone demonstrated negative results when exposed to 1, 5, and 25 ppm concentrations, while demonstrating positive result when exposed to 50 ppm concentration. However, the PBO did not show any co-genotoxic activity with the four tested synthetic pyrethroids. Results of this study will take an important place in human and environmental health with the new results for the PBO ratios in insecticide formulations.

Absence of mutagenic and recombinagenic activity of multi-walled carbon nanotubes in the Drosophila wing-spot test and Allium cepa test

In order to assess the safety of the carbon nanotubes to human health and the environment, we investigated the potential toxicity and ability of multi-walled carbon nanotubes (NT), to induce DNA damage by employing the Allium cepa genotoxicity/mutagenicity test and the Somatic Mutation and Recombination Test (SMART) in the fruitfly, Drosophila melanogaster. The results demonstrated that NT did not significantly induce genotoxic or mutagenic effects in the Allium cepa test. All concentrations evaluated in the SMART assay showed survival rates higher than 90percent, indicating the absence of chronic toxicity for NT. Furthermore, the various treatments showed no significant increase in the NT mutation and recombination frequencies in mwh/flr3 genotype compared to respective negative controls, demonstrating the absence of DNA damage caused by NT.

Investigation of the genotoxic and antigenotoxic properties of essential oils obtained from two Origanum species by Drosophila wing SMART assay

In this study, essential oils extracted from 2 species of oregano, Origanum onites L. and Origanum minutiflorum O.Schwarz & P.H.Davis, were assayed for genotoxicity using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Results indicated that there is no significant genotoxic effect of the 2 oils tested. In addition, the antigenotoxic activities of these oils against potassium dichromate (K_{2}Cr_{2}O_{7}) and cobalt chloride (CoCl_{2}) were tested. Results indicated that essential oil cotreatments were able to abolish the genotoxic effects induced by the 2 metal compounds. It is suggested that the observed effects can be linked to the antioxidant properties of the selected essential oils. Moreover, these in vivo results will contribute to the antigenotoxicity database of the 2 Origanum species used in this study.

Effects of two plant growth regulators, indole-3-acetic acid and β-naphthoxyacetic acid, on genotoxicity in Drosophila SMART assay and on proliferation and viability of HEK293 cells from the perspective of carcinogenesis

In this study, the mutagenic and recombinogenic effects of indole-3-acetic acid (IAA), a plant growth regulator naturally synthesized in plants but produced synthetically, and β-naphthoxyacetic acid (BNOA), a synthetic plant growth regulator widely used in agricultural regions, were investigated using the somatic mutation and recombination test (SMART) in Drosophila wings. The effect of the same plant growth regulators against the proliferation and viability of a human immortalized embryonic kidney HEK293 cells which is at the early stage of carcinogenesis were also examined with MTT and trypan-blue exclusion assays. For the SMART assay, two different crosses were used: a standard and a high-bioactivation (HB) cross, involving the flare-3 and the multiple wing hairs markers. The HB cross involved flies characterized by an increased cytochrome P-450-dependent bioactivation capacity, which permits the more efficient biotransformation of promutagens and procarcinogens. In both crosses, the wings of the two types of progeny, inversion-free marker heterozygotes and balancer heterozygotes, were analyzed. The results show that IAA and BNOA are not mutagenic or recombinogenic in the wing cells of Drosophila. Furthermore, neither plant growth regulator affected the proliferation rate of HEK293 cells; however, both of them induced cell death at high concentrations.

Induced DNA Damage by Dental Resin Monomers in Somatic Cells

The present in vivo study investigated the genotoxicity of four dental resin monomers: triethyleneglycoldimethacrylate (TEGDMA), hydroxyethylmethacrylate (HEMA), urethanedimethacrylate (UDMA) and bisphenol A-glycidylmethacrylate (BisGMA). The Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster was applied to analyse their genotoxicity expressed as homologous mitotic recombination, point and chromosomal mutation. SMART detects the loss of heterozygosity of marker genes expressed phenotypically on the fly's wings. This fruit fly has an extensive genetic homology to mammalians, which makes it a suitable model organism for genotoxic investigations. The present findings provide evidence that the mechanistic basis underlying the genotoxicity of UDMA and TEGDMA is related to homologous recombination and gene/chromosomal mutation. A genotoxic pattern can correspondingly be discerned for both UDMA and TEGDMA: their genotoxicity is attributed respectively to 49% and 44% of mitotic recombination, as well as 51% and 56% of mutational events, including point and chromosomal alterations. The monomer UDMA is 1.6 times more active than TEGDMA to induce mutant clones per treatment unit. BisGMA and HEMA had no statistically significant effect on total spot frequencies - suggesting no genotoxic action in the SMART assay. The clinical significance of these observations has to be interpreted for data obtained in other bioassays.

Genotoxic effects of eugenol, isoeugenol and safrole in the wing spot test of Drosophila melanogaster

In the present study, the phenolic compounds eugenol, isoeugenol and safrole were investigated for genotoxicity in the wing spot test of Drosophila melanogaster. The Drosophila wing somatic mutation and recombination test (SMART) provides a rapid means to evaluate agents able to induce gene mutations and chromosome aberrations, as well as rearrangements related to mitotic recombination. We applied the SMART in its standard version with normal bioactivation and in its variant with increased cytochrome P450-dependent biotransformation capacity. Eugenol and safrole produced a positive recombinagenic response only in the improved assay, which was related to a high CYP450-dependent activation capacity. This suggests, as previously reported, the involvement of this family of enzymes in the activation of eugenol and safrole rather than in its detoxification. On the contrary, isoeugenol was clearly non-genotoxic at the same millimolar concentrations as used for eugenol in both the crosses. The responsiveness of SMART assays to recombinagenic compounds, as well as the reactive metabolites from eugenol and safrole were considered responsible for the genotoxicity observed.

Effect of vanillin on toxicant‐induced mutation and mitotic recombination in proliferating somatic cells of Drosophila melanogaster

Vanillin (VA; C8H8O3) is a flavoring agent that in previous studies has both increased and decreased the genotoxicity of chemical agents, depending on the nature of both the agent and the genetic event measured. The ability of VA to modulate the mutagenicity and recombinogenicity of three different monoalkylating agents, N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU), and ethyl methanesulfonate (EMS), and the intercalating agent bleomycin (BLEO) was examined using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. While neither the mutagenicity nor the recombinagenicity of ENU or MNU was modified by posttreatment with VA, EMS-induced genetic toxicity was enhanced by as much as 30%. This overall enhancement included a synergistic increase in mitotic recombination and a lesser decrease in mutation. Posttreatment with VA also produced an increase in the genotoxicity of BLEO, which was characterized by increases of 120% and 180% for 0.5% and 1% VA, respectively. This enhancement was restricted to an increase in recombinational events, since no alteration in BLEO-induced mutation was observed. The data suggest that the major VA-modulatory action on genotoxicity in D. melanogaster is related to its synergistic effects on somatic recombination, which has a greater consequence on overall genotoxicity than its antimutagenic effects. Since the SMART assay is specifically sensitive to mitotic crossing-over, our data suggest that VA promotes toxicant-induced homologous recombination, at least in the proliferative cells of Drosophila.