XRCC1 gene variants and possible links with chromosome aberrations and micronucleus in active and passive smokers

Tobacco addiction is a major risk for diseases such as cancers, heart attack, etc. Tobacco smoke constitutes environmental toxins that are the major preventable leading cause of death worldwide. We investigated the influence of tobacco smoke on cytogenetic parameters (chromosomal aberrations and micronuclei) and the influence of XRCC1 arg399gln polymorphism on the cytogenetic parameters of the exposed subjects. The cases for this study include active and passive smokers. They were divided into three groups in accordance with duration of exposure to tobacco smoke. We observed changes in the frequency of chromosomal aberrations and micronuclei among the exposed subjects and controls. Of the three groups of exposed subjects, group III of active smokers and group III of passive smokers showed higher number of chromosomal aberrations and micronuclei when compared to controls, group I and group II of active and passive smokers. The XRCC1 arg399gln polymorphic variant gln/gln, influenced the extent of genotoxic damage in chromosomes and frequency of in micronuclei the three variants (arg/arg, arg/gln and gln/gln), gln/gln harbored significantly (P < 0.05) higher number of aberrations than the arg/arg and arg/gln. In this context, the results observed in our study indicated that the single nucleotide polymorphism on XRCC1codon 399 influenced the frequencies of chromosomal aberrations and micronuclei.     

Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in human lymphocytes in vitro

Naringin is a flavonoid found in grapefruit and other citrus fruits that shows antioxidant activity. The aim of the present study was to determine the anti-genotoxic and protective effects of naringin on the chemotherapeutic/radiomimetic agent bleomycin (BLM) in human blood lymphocyte cultures in vitro using micronucleus test and chromosomal aberrations (CA) assay. We tested the three doses of naringin (1, 2, 3?µg/mL) and a single dose of BLM (20?µg/mL). BLM significantly increased the total CAs and micronucleus frequency at a concentration of 20?µg/mL. Naringin did not show any toxicity in doses of 1, 2, and 3?µg/mL. Combined treatments of BLM and naringin (2 and 3?µg/mL) significantly reduced micronucleus formation. Naringin dose-dependently decreased the total chromosome aberrations frequency induced by BLM. These results indicate that naringin could prevent BLM (20?µg/mL)-induced genotoxicity.     

Effect of genetic polymorphism of GSTM1 and GSTT1 genotypes on cytogenetic biomarkers among coaltar workers

Chromosomal aberrations (CAs) in peripheral blood lymphocytes and micronuclei (MN) in exfoliated buccal cells have been used for decades as cytogenetic biomarkers to investigate genotoxicity among occupationally or environmentally exposed population. In our study, we investigated the association of increased cytogenetic damage with genetic polymorphism in glutathione-S transferase genotypes among occupationally exposed 115 coaltar workers and 105 unexposed controls. We found higher mean value of chromosome aberrations (chromatid type-2.01 ± 1.76; chromosomal type-2.22 ± 1.73) and buccal micronuclei (BMN-7.10 ± 1.56) in exposed subjects when compared to referents (chromatid type-0.82 ± .51; chromosomal type-0.87 ± .54; BMN-5.09 ± 2.88). We observed that individuals having null genotype of GSTM1 and GSTT1 have significantly higher frequency of CAs and MN. Despite of small sample size, our findings suggest a significant association between polymorphism of glutathione-S transferase genotypes and cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens.     

Evaluation of cytogenetic and DNA damage induced by the antidepressant drug-active ingredients,trazodone and milnacipran,in vitro

Trazodone and milnacipran are the active antidepressant drugs that are being used in the treatment of psychiatric disorders. In this study, the in vitro genotoxic effects of trazodone and milnacipran have been determined in human peripheral blood lymphocytes by using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and comet assays. 3.13; 6.25; 12.50; 25.00; 50.00; and 75.00?μg/mL concentrations of trazodone and 2.50; 5.00; 10.00; 20.00; 30.00; and 40.00?μg/mL concentrations of milnacipran were used. Trazodone and milnacipran significantly increased the frequency of CAs and SCEs compared with the control. Both of the active ingredients raised the MN frequency in a dose-dependent manner. Mitotic index was significantly decreased, but replication and nuclear division indices were not affected at all treatments. Trazodone was statistically increased the mean comet tail intensity, tail length, and tail moment at three concentrations (6.25; 12.50; and 25.00?μg/mL) compared with control. Two highest concentrations (50 and 75?μg/mL) of trazodone were toxic in the comet assay. Milnacipran increased the comet tail intensity, tail length, and tail moment at all concentrations. It is concluded that trazodone and milnacipran have clastogenic, mutagenic, and cytotoxic effects on human lymphocytes in vitro.     

Mutagenicity tests of the antithyroid agent thiamazole. Cytogenetic studies on male mice

The mutagenic potential of thiamazole, an antithyroid agent, was investigated by an in vivo cytogenetic test and was compared with those of mitomycin C and vincristine. These drugs were subcutaneously injected into slc-ICR male mice either as a single dose or as multiple doses for 5 successive days. Thiamazole (90 or 180 mg/kg) did not increase the number of micronuclei in bone marrow cells. This drug also did not induce chromosomal aberrations in spermatogonium, spermatocyte, or bone marrow cells. On the other hand, mitomycin C (3.0 mg/kg) increased the appearance of chromosomal aberrations and micronuclei. Vincristine (0.2 mg/kg) induced bone marrow cells with a so called large micronucleus (d greater than or equal to D/4). These results suggest that thiamazole may not have significant effects on the genetic systems of mice.     

UV-filter benzophenone-3 inhibits agonistic behavior in male Siamese fighting fish (<Emphasis Type="Italic">Betta splendens</Emphasis>)

Benzophenone-3 (BP-3) is a widely used organic UV-filter compound. Despite the frequent occurrence of BP-3 in aquatic environments, little is known about its effect on fish behavior. The aim of this study was to investigate the endocrine disrupting effects of BP-3 in male fighting fish (Betta splendens) with a focus on agonistic behavior. Male fighting fish were exposed to 10, 100, and 1000 μg/L BP-3, as well as a solvent control (0.1 % ethanol) and a positive control (100 ng/L 17α-ethynylestradiol, EE2), for 28 days. At the beginning and the end of exposure, standard length and body mass of the fish were measured for calculating the condition factor (CF). In addition, spontaneous swimming activity (total distance moved) and agonistic behavior (maximum velocity and duration of opercular display in front of a mirror) were also quantified. At the end of exposure, the fish gonads were sampled for gonadosomatic index (GSI) measurement and histology. After the exposure, CF was significantly decreased in the 1000 μg/L BP-3 groups. Spontaneous swimming activity was not affected. However, maximum velocity was significantly reduced in the EE2 and 1000 μg/L BP-3 treatments; duration of opercular display was significantly decreased in the EE2 and 10 and 1000 μg/L BP-3 treatments. GSI was not significantly different between groups. There was a slight but statistically significant decrease of relative proportion of mature spermatozoa in testicular tissue in the 100 μg/L BP-3 treatment. Collectively, our results demonstrate that BP-3 can disrupt agonistic behavior of male fighting fish, indicating the endocrine disrupting activity of this compound.     

Assessment of acetamiprid-induced genotoxic effects in bone marrow cells of Swiss albino male mice

Acetamiprid (ACE), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations (CA) assay was utilized to assess the genotoxic effects of ACE in bone marrow of Swiss albino male mice. Acetamiprid was administered i.p. daily at 4.6 and 2.3?mg/kg/day along with 3% gum acacia as negative control for 60 and 90?days and cyclophosphamide (50?mg/kg b.wt.) as positive control. ACE treatment resulted in a dose-dependent increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. The increased micronuclei formation in total erythrocyte cells (immature PCEs and mature NCEs) was observed only at higher dose level (4.6?mg/kg b.wt.) administered for 90?days. The test also indicated the cytotoxic effect of higher dose level of pesticide by PCE/NCE ratio. The number of chromosomal aberrations were increased in the pesticide treated group compared to the negative control group, although significant increase was observed only in the group exposed to higher dose level of pesticide for both 60 and 90?days. Thus, daily exposure of ACE at a dose level of 4.6?mg/kg body weight for 60 and 90?days caused genotoxic and cytotoxic effects on the somatic cells of Swiss albino male mice.     

N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced in vivo clastogenicity: protective effects of aqueous neem leaf extract

We evaluated the modifying effects of aqueous neem leaf extract on the in vivo clastogenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a potent gastric carcinogen by quantitation of micronuclei and chromosomal aberrations in metaphase cells from the bone marrow of male Wistar rats. Intraperitoneal injection of MNNG (40 mg/kg body weight) induced a significant increase in the frequency of micronuclei and chromosomal aberrations. Pretreatment with aqueous neem leaf extract (100 mg/kg body weight) significantly reduced MNNG-induced increase in micronuclei and chromosomal aberrations. These results reveal the chemoprotective potential of aqueous neem leaf extract against the clastogenic effects of MNNG.     

Fumonisins in foods from Cordoba (Argentina), presence and genotoxicity.

Fumonisins B(1), B(2)yB(3) (FB(1), FB(2)yFB(3)), are a group of toxins produced by different mold species, Fusarium moniliforme and Fusarium proliferatum being the most important ones. Its compounds were tested in chromosome aberrations (CA), sister chromatid exchange (SCE), and micronucleus (MN) in human lymphocytes, and, in Allium cepa (onion), the chromosomal aberrations (CA) assay was used. Moreover, the presence of fumonisins and their producer moulds was determined in different food substrata in Cordoba city, Argentina. Cytogenetic studies using FB(1), FB(2) and FB(3) levels gave positive results for the higher concentrations (5 and 10mug/g) with FB(1). As regards the cytogenetic aspect of FB(1), we found an increase in the incidence of genetic damage measured by chromosomal aberrations, sister chromatid exchange, micronuclei and chromosomal aberrations in Allium cepa. These results indicate that human lymphocytes cells and plants cells (Allium cepa) have a very sensitive cellular response to the mycotoxin fumonisin B(1) as observed at the highest concentrations.     

Genotoxic evaluation of terbinafine in human lymphocytes in vitro

Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0?μg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0?μg/ml, 25.0?μg/ml, 50.0?μg/ml and 100.0?μg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α?=?0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.     

Antidiabetic and antioxidant potency evaluation of different fractions obtained from Cucumis prophetarum fruit

Abstract

Context: Cucumis prophetarum Linn. (Cucurbitaceae) fruit is used for inflammatory-related problems and is proved to be possessing anticancer and hepatoprotective effects.

Objective: The present investigation was to study the effect of different fractions of C. prophetarum on antidiabetic and antioxidant activity.

Materials and methods: Aqueous crude extract (CE) of C. prophetarum fruits was fractionated into water soluble fraction 1 (F1), chloroform fraction 2 (F2), basic fraction 3 (F3), and neutral fraction 4 (F4) by acid–base extraction. CE and its fractions at different doses (0.02–0.1?mg/mL) were subjected to antidiabetic (α-amylase and α-glucosidase inhibition assays) and antioxidant (DPPH, superoxide radical scavenging (SO) and metal chelation) evaluation.

Results: F1 exhibited effective antidiabetic activity (p?<?0.05) with an IC₅₀ value of 20.6 and 59.9?µg/mL. The activity decreased in the order of CE?>?F4?>F3?>?F2, according to α-amylase assay, which were the same, with the exception of the rank order of F4 and CE, as the α-glucosidase assay. Furthermore, F1 (IC₅₀?=?73?µg/mL) showed better reducing ability than CE?>F4?>F2?>?F3 (IC₅₀?=?78–272?µg/mL), according to the DPPH assay. In SO and metal chelation assays, F1 showed the highest activity (IC₅₀?=?101 and 147?µg/mL), respectively; the activity decreased in the order of CE?>F4?>F3?>?F2 (IC₅₀?=?126–469?µg/mL) for SO and 194–944?µg/mL for metal chelation assay.

Conclusion: The results indicate that F1 possesses potent in vitro antidiabetic and antioxidant activities.     

Chitosan Oligosaccharide inhibits203HgCl2-induced genotoxicity in mice: Micronuclei occurrence and chromosomal aberration

The purpose of this study was to investigate the safety of chitosan oligosaccharide and the effects of chitosan oligosaccharide on mercury induced genotoxicity in mice using the micronuclei and chromosome aberration. The micronuclei test was performed by microscopic examination (x1,000, stained using a May-Grunwald solution) after administering 0.01, 0.1, and 1% (10 mg/mL) chitosan oligosaccharide for 7, 60, and 180 days ad libitum in mice. Total micronuclei of 1,000 polychromatic erythrocytes were recorded for each group. There was no difference between the untreated and experimental groups. The intake periods and concentrations of chitosan oligosaccharide did not affect the occurrence of micronuclei in bone marrow cells (P>0.05). The chromosomal aberration test was performed by microscopic examination (x1,000, stained using a 4% Giemsa solution) after administering the same concentration of chitosan oligosaccharide to mice, in F1, F2, F3 generations and parents. The frequency of chromosomal aberrations was defined as [Ydr = (D+R)/total number of counted lymphocytes]. Similar to the micronuclei test, there was no difference between the untreated and treated groups. These results showed that the intake periods and concentrations of chitosan oligosaccharide did not affect chromosomal aberrations in bone marrow cells (P>0.05). To investigate the effect of chitosan oligosaccharide on mercury-induced chromosome aberration, mice in each condition were supplied with 203HgCl2 and chitosan oligosaccharide ad libitum. Chitosan oligosaccharide significantly inhibited 203HgCl2-induced chromosome aberration in mice. Based on the results of this study, it may be concluded that the chitosan oligosaccharide is a nontoxic material that could be used as a suppressor of heavy metal-induced genotoxicity.     

Cytogenetic effects of trifluoperazine in mice

The cytogenetic effects of trifluoperazine have been studied in male Swiss albino mice using the micronucleus test, chromosomal analysis in germ cells and a sperm morphology assay. The mice were treated by gavage with 80, 120 or 160 micrograms trifluoperazine/kg, divided in each case into two equal doses given 24 hr apart. The dose levels were selected on the basis of standard human therapeutic dosage. Compared with the findings in control mice dosed with distilled water, there were significant increases in the frequency of micronuclei, of chromosomal aberrations in the spermatocytes and of abnormal sperms, at all the levels of trifluoperazine treatment.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

Protective effect of S-allylcysteine and lycopene in combination against N-methyl-N'-nitro-N-nitrosoguanidine-induced genotoxicity

Chemoprotection by diet-derived antioxidants has emerged as a cost-effective approach in preventing genotoxicity and carcinogenicity. In this study, we investigated the protective effects of S-allylcysteine (SAC) and lycopene against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity. Quantification of bone marrow micronuclei and chromosomal aberrations in male Wistar rats was used to monitor the protective effects of SAC and lycopene. Intragastric administration of MNNG (40 mg/kg) induced a significant increase in the frequency of micronuclei and chromosomal aberrations. Although pretreatment with SAC and lycopene significantly reduced the frequency of MNNG-induced bone marrow micronuclei and chromosomal aberrations, the combination of SAC and lycopene exerted a greater protective effect. These findings indicate that antioxidants such as SAC and lycopene, are effective chemoprotective agents against genotoxicity and carcinogenicity especially when used in combination.     

Antimutagenic potential of Solanum lycocarpum against induction of chromosomal aberrations in V79 cells and micronuclei in mice by doxorubicin

Solanum lycocarpum A. St. Hil. (Solanaceae) is a hairy shrub or small much-branched tree of the Brazilian Cerrado. S. lycocarpum fruits are commonly used in traditional medicine in powder form or as folk preparations for the treatment of diabetes and obesity, as well as for controlling cholesterol levels. The aim of the present study was to chemically characterize the hydroalcoholic extract (SL) of S. lycocarpum by determination of total flavonoids and total poyphenols and quantification of steroidal alkaloids, as well as to evaluate its mutagenic and/or antimutagenic potential on V79 cells and Swiss mice using chromosomal aberrations and bone marrow micronucleus assays, respectively. Three concentrations of SL (16, 32, and 24?μg/mL) were used for the evaluation of its mutagenic potential in V79 cells and four doses (0.25, 0.50, 1.0, and 2.0?g/kg body weight) were used for Swiss mice. In the antimutagenicity assays, the different concentrations of SL were combined with the chemotherapeutic agent doxorubicin (DXR). HPLC analysis of SL gave contents of 6.57?%?±?0.41 of solasonine and 4.60?%?±?0.40 of solamargine. Total flavonoids and polyphenols contents in SL were 0.04 and 3.60?%, respectively. The results showed that not only SL exerted no mutagenic effect, but it also significantly reduced the frequency of chromosomal aberrations induced by DXR in both V79 cells and micronuclei in Swiss mice at the doses tested.     

Cytogenetic and developmental toxicity of bisphenol A and bisphenol S in Arbacia lixula sea urchin embryos

Bisphenol S (BP-S) is one of the most important substitutes of bisphenol A (BP-A), and its environmental occurrence is predicted to intensify in the future. Both BP-A and BP-S were tested for adverse effects on early life stages of Arbacia lixula sea urchins at 0.1 up to 100?µM test concentrations, by evaluating cytogenetic and developmental toxicity endpoints. Embryonic malformations and/or mortality were scored to determine embryotoxicity (72?h post-fertilization). It has been reported in academic dataset that bisphenols concentration reached μg/L in aquatic environment of heavily polluted areas. We have chosen concentrations ranging from 0.1–100?μM in order to highlight, in particular, BP-S effects. Attention should be paid to this range of concentrations in the context of the evaluation of the toxicity and the ecological risk of BP-S as emerging pollutant. Cytogenetic toxicity was measured, using mitotic activity and chromosome aberrations score in embryos (6?h post-fertilization). Both BP-A and BP-S exposures induced embryotoxic effects from 2.5 to 100?µM test concentrations as compared to controls. Malformed embryo percentages following BP-A exposure were significantly higher than in BP-S-exposed embryos from 0.25 to 100?µM (with a ~5-fold difference). BP-A, not BP-S exhibited cytogenetic toxicity at 25 and 100?µM. Our results indicate an embryotoxic potential of bisphenols during critical periods of development with a potent rank order to BP-A vs. BP-S. Thus, we show that BP-A alternative induce similar toxic effects to BP-A with lower severity.

     

Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex

Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae).

Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers.

Materials and methods The anti-proliferative activity of the extracts (10–70?μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5–7.5?mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200?mg/kg) or indomethacin (50?mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods.

Results Flower extracts contained a high level of polyphenolics (17.10–52.70?mg GAE/g) and flavonoids (74.20–100.60?mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC₅₀ value: 12.50–27.10?μg/mL), DPPH^? radical-scavenging (IC₅₀ value: 0.20–0.40?mg/mL), Fe^3+?reducing (EC₅₀ value: 0.10–0.14?mg/mL) and Fe^2+?chelating (IC₅₀ value: 0.20–0.60?mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC₅₀ value: 62.0–63.25?μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC₅₀ value: 2.97?mg/mL) and reduced the paw oedema in mice (from 0.38?±?0.01 to 0.24?±?0.01?cm), 4?h post-carrageenan challenge.

Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer.     

The nature of chromosomal aberrations detected in humans exposed to benzene

Benzene is an established cause of human leukemia that is thought to act by producing chromosomal aberrations and altered in cell differentiation. In several recent studies increased levels of chromosomal aberrations in peripheral blood lymphocytes were correlated with a heightened risk of cancer, especially hematological malignancies. Thus, chromosomal aberrations may be a predictor of future leukemia risk. Previous studies exploring whether benzene exposure induces chromosomal aberrations have yielded mostly positive results. However, it remains unclear whether the chromosomal aberrations induced by benzene occur in a distinct pattern. Here, we thoroughly review the major chromosome studies published to date in benzene-exposed workers, benzene-poisoned and preleukemia patients, and leukemia cases associated with benzene expose. Although three cytogenetic markers (chromosomal aberrations, sister chromatid exchanges, and micronuclei) are commonly examined, our primary focus is on studies of chromosomal aberrations, because only this marker has so far been correlated with increased cancer risk. This review surveys the published literature, analyzes the study results, and discusses the characteristics of effects reported. In most studies of currently exposed workers, increases in chromosomal aberrations were observed. However, due to the relatively small number of affected individuals and variability in the reported aberrations, firm conclusions cannot be made about the involvement of specific chromosomes or chromosome regions. Further, in leukemia cases associated with benzene exposure, there is no evidence of a unique pattern of benzene-induced chromosomal aberrations in humans. Leukemia cases associated with benzene exposure are, however, more likely to contain clonal chromosome aberrations then those arising de novo in the general population.     

Cytotoxicity,mutagenicity, and antimutagenicity of the gentisic acid on HTC cells

Gentisic acid (GA) exhibits antioxidant, anti-inflammatory, and antibiotic activities. This substance can be found in citrus fruits, grapes, olive oil, and peas. Considering that there are few studies in the literature on the toxicity of GA, the present work aimed to investigate its cytotoxic, mutagenic, and antimutagenic activities on HTC cells. GA was diluted in culture medium at the final concentration of 0.08, 0.16, 0.8, 1.6, and 8?μg/mL. The cytotoxicity was determined by the MTT assay and Trypan Blue exclusion method, with methyl methanesulfonate and doxorubicin as positive controls, respectively. The cytokinesis-block micronucleus assay determined the mutagenic/antimutagenic activity with benzo[a]pyrene as positive control. Negative control received culture medium only. GA (0.08–8?μg/mL) was not cytotoxic to HTC cells by the MTT assay nor the Trypan Blue exclusion method as no statistical difference was observed when compared to the control. Concentration of 0.08 and 0.8?μg/mL showed no mutagenic or clastogenic effects, as no significant micronuclei inductions were observed, different from 8?μg/mL, that was mutagenic. Furthermore, none of the concentrations presented an antiproliferative activity. The antimutagenic activity of GA (0.08?μg/mL) was observed at the simultaneous treatment, as it reduced the frequency of micronuclei by 76% (24?h) and 79% (48?h). Although pre- and post-treatments were not statistically different from the mutagen, they reduced the induced-damage by 11% and 21%, respectively. The present study indicated the absence of cytotoxicity and antiproliferative activities of GA, in addition to their antimutagenic/protective effects that may contribute to human health.