Sister-chromatid exchanges and chromosome aberrations in lymphocytes from monkeys exposed to ethylene oxide and propylene oxide by inhalation

The ability of long-term exposures to inhaled ethylene oxide (EO) and propylene oxide (PO) to induce sister-chromatid exchanges (SCEs) and chromosome aberrations in peripheral lymphocytes of monkeys was investigated. Five groups of adult male cynomolgus monkeys were exposed at 0 (shared control), 50, or 100 ppm EO, and at 100 or 300 ppm PO (7 hr/day, 5 days/week) for 2 years. EO exposures at 50 and 100 ppm resulted in statistically significant increases in sister-chromatid exchange rates and in the incidence of chromosome aberrations in monkey lymphocytes. Both EO-exposed groups had increased numbers of SCEs/metaphase compared to controls, with the SCEs/metaphase of the EO 100 ppm group also significantly elevated versus the EO 50 ppm group. Variability of SCEs/metaphase within each monkey increased even more than the increase in total SCEs/metaphase group with increasing EO exposure. Chromatid-type aberrations were also significantly increased for both EO 50 and EO 100 ppm groups compared to controls. Statistically significant increases in the number of chromosome-type aberrations (excluding gaps) were found only in the EO 100 ppm group. Combined chromatid- and chromosome-type aberrations were increased in both EO 50 and EO 100 ppm groups. No group differences in the number of gaps were found. In lymphocytes from monkeys exposed at 100 and 300 ppm PO, there were no group differences compared to controls for any variable-chromatid or chromosome-type aberrations, gaps, or SCEs/metaphase. These results indicate that EO is a more potent clastogen than PO and demonstrate, for the first time, statistically significant effects of EO on both SCEs and chromosome aberrations in lymphocytes of nonhuman primates.     

Analysis of cytogenetic damage in rat lymphocytes following in vivo exposure to nitrobenzene

Male F-344 rats were exposed to target concentrations of 0, 5, 16, or 50 ppm nitrobenzene for 6 h/day, 5 days a week, for 21 days during a 29-day period. Isolated spleen (ISLs) and peripheral blood lymphocytes (PBLs) were cultured in the presence of 2 microM 5-bromodeoxyuridine and scored for sister-chromatid exchange (SCE) and PBLs were also scored for chromosome aberrations. No significant increase in SCE frequency or chromosome aberrations was found in the PBLs, and no significant increase in SCEs was observed in the ISLs at any of the concentrations. Thus, cytogenetic analysis of ISLs and PBLs provide no evidence of a genotoxic potential for nitrobenzene.     

Cytogenetic studies on preimplantation mouse embryos exposed to methylnitrosourea in vivo

Since exposure of mice to methylnitrosourea (MNU) during the preimplantation period can induce malformations and an increased postnatal death rate, direct embryotoxic effects were studied in preimplantation embryos shortly after treatment of pregnant mice on days 2 and 3 of gestation with single i.p. injections of 2.5, 5.0, and 10.0 mg/kg MNU. Embryos exposed to MNU for 24 h after treatment on day 2 showed a significant reduction of cell number and induction of sister chromatid exchange (SCE) frequency, but no structural chromosomal aberrations or inhibition of development during culture. Embryos exposed to MNU in vivo for 3 h on day 3 showed significantly reduced cell numbers, a significant inhibition of development in culture, and an increase in structural chromosome aberrations. Due to the high cytotoxicity of MNU, determination of SCE was not possible. The results indicate that MNU reaches preimplantation mouse embryos shortly after maternal treatment and that malformations seen at term and postnatal effects are probably induced by the direct action of MNU on early embryos. Furthermore, the importance of the time interval chosen for evaluation of toxicologic endpoints in preimplantation embryos is demonstrated.     

In vivo cytogenetic studies on mice exposed to Orange G, a food colourant

Orange G, a monoazo dye, used as a food colourant, was evaluated with in vivo cytogenetic assays to determine its genotoxicity. Swiss albino male mice were exposed to Orange G through intraperitoneal injections. Bone marrow cells isolated from femora were analyzed for sister chromatid exchanges (SCE) and chromosome aberrations. The results showed that the incidence of SCEs and chromosome aberrations were significantly higher than controls at certain concentrations. 25 mg/kg of Orange G was found to be the minimum effective dose for the induction of both SCEs and chromosome aberrations. Orange G is thus found to be clastogenic and genotoxic in vivo in mice.     

Increased frequency of chromosomal aberrations and sister chromatid exchanges in peripheral lymphocytes of radiology technicians chronically exposed to low levels of ionizing radiations

Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) frequencies were estimated in peripheral lymphocytes from 21 radiology technicians, and from 21 non-exposed control subjects. We exclusively considered individuals who neither smoke nor consume drugs or alcohol for a period of at least two years prior to the analysis. Significant differences were found between exposed and controls in terms of SCEs and CAs frequencies.Technicians showed a significant higher number of high-frequency individuals (HFIs) with respect to the control group. Nevertheless, the mean frequency of SCEs observed among technician HFIs did not significantly differ with respect to that observed among control HFIs. Vice versa, the non-HFIs belonging to technicians group showed a statistically higher difference in the SCEs/NSM value with respect to the non-HFIs belonging to control group. Since the differences in the SCEs frequencies between the two groups are due to non-HFIs, our results seem to indicate a general genotoxic effect of the IR, not affected by HFIs.Among technicians, the level of chromosome damage correlated neither with years of radiation exposure nor with the age of the subjects. Vice versa, in the control group, a positive correlation was found between the number of SCEs and age. In both samples the gender status did not influence the frequencies of CAs and SCEs.Our results suggest that chronic long-term exposure to low doses of ionizing radiation could increase the CAs and SCEs frequencies. This study reinforces the relevance of the biomonitoring of hospital workers chronically exposed to ionizing radiation.     

EVALUATION OF ADVERSE OCULAR EFFECTS OF 5-FLUOROURACIL BY USING HUMAN CORNEAL EPITHELIAL CELL CULTURES

5-Fluorouracil (5-FU) is commonly used in ophthalmology for suppressing fibroblast activity after glaucoma surgery. Adverse effects on corneal epithelial cells have been reported to relate to 5-FU therapy. The effects of 5-FU were evaluated in vitro on SV40-immortalized human corneal epithelial cell (HCE) cultures with two cytotoxicity tests: WST-1 assay as an index of cell proliferation, and lactate dehydrogenase (LDH) assay as an index of plasma membrane integrity. The cells were exposed to 5-FU with various concentrations in serum-free medium and in medium containing 15 % (v/v) fetal bovine serum (FBS) for 1, 24, 48 and 72 hours. One-hour exposure had no effects on HCE cells. Longer exposures caused dose-dependent inhibition of cell proliferation. Exposure to 5 mg/ml 5-FU lowered cell number to 50 % of controls after 24-hour treatment and resulted to complete cell death after 72 hours. Serum protected the cells for 24 hours, but after longer exposure times the protective nature of serum disappeared. 5-FU had only minor effects on LDH release. The LDH leakage was at its peak after 48-hour treatment.     

Determination of chromosome aberrations in workers in a petroleum refining factory

Human exposure to benzene is derived occupationally from the petrochemical and petroleum refining industries. This study was performed to determine whether the frequencies of chromosome aberrations in workers exposed to low levels of benzene in a petroleum refining factory were elevated compared to an unexposed control group. The study population was comprised of 178 exposed workers and 36 unexposed workers. The frequencies of chromatid deletions and total chromosome aberrations in workers exposed to benzene were significantly higher compared to the unexposed control group. The frequency of total chromosome aberration was 4.20 per 500 metaphase cells in the exposed workers, whereas the frequency was 2.24 per 500 metaphase cells in the unexposed control group. The frequencies of total chromosome aberrations were significantly associated with benzene concentration after adjusting for confounding variables such as age, smoking status, and alcohol intake. The frequencies of chromosome aberrations were significantly increased in workers with low white blood cell counts (below 4000 cells/mm3) compared to those with high white blood cell counts (above 4000 cells/mm3). A reduced white blood cell count (below 4000/mm3) is suggestive of chronic exposure to benzene. In conclusion chronic benzene exposure and preclinical signs, such as reduced white blood cell counts, may be monitored by chromosome aberrations analysis.     

Studies on the acute toxicity primary irritancy and genotoxic potential of 1,3,5-triacryloylhexahydro-s-triazine (TAHT)

TAHT (1,3,5-triacryloylhexahydro-s-triazine), a reactive chemical coupling agent, was highly toxic following a single peroral dose of an aqueous suspension (10% w/v) to Wistar rats, or following application of TAHT in dichloromethane (DCM) solution (10% w/v) to covered skin of New Zealand rabbits. It was moderately toxic when applied dermally as an aqueous paste. Ocular contact with 25 mg of TAHT in a 5% aqueous suspension, or of 0.5 mg of TAHT in a 10% (w/v) solution in DCM, produced severe corneal damage, iritis and blepharo-conjunctivitis. A 30-min exposure of uncovered rabbit skin to 1 mg of TAHT in a 10% (w/v) aqueous suspension produced only slight skin irritation. However, 24-h exposures to TAHT on covered skin produced erythema, edema, ecchymoses, scabs, and death depending upon dosage and vehicle. In vitro genotoxicity studies revealed no positive effects upon gene mutations (HGPRT locus) or on sister chromatid exchanges (SCEs) of CHO cells exposed to TAHT with and without a rat-liver S9 metabolic activation system. TAHT did not increase the levels of [3H]thymidine incorporation in a test for unscheduled DNA synthesis with primary rat hepatocytes. In contrast, substantial increases in the number of chromosome breaks and rearrangements were observed in chromosome preparations used for the SCE analyses. The clastogenic activity of TAHT was confirmed in an in vitro chromosome aberration test with CHO cells. Treatment-related increases in chromosome breakage were observed at two independent sampling times and positive effects did not depend upon the presence or absence of a metabolic activation system. Clastogenic activity of TAHT was also demonstrated in vivo in a micronucleus test using mouse peripheral polychromatic erythrocytes. Significant, treatment-related increases in micronucleated polychromatic erythrocytes were obtained at two of three sampling times. The high degree of mammalian toxicity, severe eye irritancy and the in vitro and in vivo clastogenicity indicate that TAHT should be handled as a hazardous material using suitable caution and protective equipment.     

The effects of food protector biphenyl on sister chromatid exchange, chromosome aberrations, and micronucleus in human lymphocytes

The aim of this study was to determine the possible genotoxic effects of biphenyl (E230), which is used as an antimicrobial agent in food by using sister chromatid exchanges (SCEs), chromosome aberrations (CAs), and micronucleus (MN) tests in human peripheral lymphocytes. The human peripheral lymphocytes were treated with four concentrations of biphenyl (10, 30, 50, and 70 microg/mL) for 24- and 48-h treatment periods. In the present study, biphenyl significantly increased the frequency of SCEs, CAs, and the frequency of MN when compared with both untreated control and solvent (dimethyl sulfoxide) control. The inductions of these abnormalities were in a dose-dependent manner. Biphenyl was capable to induce the structural CAs instead of numerical CAs. Biphenyl also showed a cytotoxic effect by decreasing the replication index at the highest two concentrations for 48 h and nuclear division index at the highest two concentrations for the 24- and 48-h treatment periods. However, biphenyl did not affect the mitotic index (MI).     

The Effects of Food Protector Biphenyl on Sister Chromatid Exchange,Chromosome Aberrations,and Micronucleus in Human Lymphocytes

The aim of this study was to determine the possible genotoxic effects of biphenyl (E230), which is used as an antimicrobial agent in food by using sister chromatid exchanges (SCEs), chromosome aberrations (CAs), and micronucleus (MN) tests in human peripheral lymphocytes. The human peripheral lymphocytes were treated with four concentrations of biphenyl (10, 30, 50, and 70 μg/mL) for 24- and 48-h treatment periods. In the present study, biphenyl significantly increased the frequency of SCEs, CAs, and the frequency of MN when compared with both untreated control and solvent (dimethyl sulfoxide) control. The inductions of these abnormalities were in a dose-dependent manner. Biphenyl was capable to induce the structural CAs instead of numerical CAs. Biphenyl also showed a cytotoxic effect by decreasing the replication index at the highest two concentrations for 48 h and nuclear division index at the highest two concentrations for the 24- and 48-h treatment periods. However, biphenyl did not affect the mitotic index (MI).     

Genotoxic, cytotoxic, developmental and survival effects of tritiated water in the early life stages of the marine mollusc, Mytilus edulis

Using an integrated approach linking different levels of biological organisation, the genotoxic, cytotoxic, developmental and survival impact of tritiated water (HTO) were investigated in the embryo-larvae of marine mollusc Mytilus edulis. One-hour-old embryos were exposed to a range of concentrations (0.37-370 kBq ml(-1)) of HTO, which delivered a dose between 0.02 and 21.41 mGy over the exposure period for different end points. Detrimental effects, if any, were monitored at different levels of biological organisation (i.e. DNA, chromosomal, cellular and individual). Genotoxic effects were assessed using molecular and cytogenetic approaches which included analysis of random amplified polymorphic DNA (RAPD), induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (Cabs). Cytotoxic effects were evaluated by determining the proliferative rate index (PRI) of the embryo-larval cells. Developmental and survival effects were also monitored every 24 h up to 72 h. Results in general indicated that HTO significantly increased cytogenetic damage, cytotoxicity, developmental abnormalities and mortality of the embryo-larvae as a function of concentration or radiation dose. The analysis of RAPD profiles also revealed qualitative effects in the HTO exposed population compared to controls. However, while the embryo-larvae showed dose or concentration dependent effects for mortality, developmental abnormalities and induction of SCEs, the dose-dependent effects were not apparent for Cabs and PRI at higher doses. The study contributes to our limited understanding of the impact of environmentally relevant radionuclides on non-human biota and emphasises the need for further investigations to elucidate potentially long term damage induced by persistent, low levels of other radionuclides on commercially and ecologically important species, in order to protect human and ecosystem health.     

Tracheal and bronchoalveolar permeability changes in rats inhaling oxidant atmospheres during rest or exercise

Permeability of tracheal and bronchoalveolar airways of rats was measured and used to examine the effects of inhaled oxidant-containing atmospheres. The atmospheres studied were (a) ozone (O3) at 0.6 ppm (1.2 mg/m3) or 0.8 ppm (1.6 mg/m3); (b) nitrogen dioxide (NO2) at 6 ppm (11.3 mg/m3) or 12 ppm (22.6 mg/m3); (c) O3 + NO2 at 0.6 ppm (1.2 mg/m3) and 2.5 ppm (4.7 mg/m3), respectively; and (d) a 7-component particle and gas mixture (complex atmosphere) representing urban air pollution in a photochemical environment. The rats were exposed for 2 h. The effects of exercise during exposure were evaluated by exposing additional groups in an enclosed treadmill. Exposure of resting rats to 0.8 ppm O3 increased tracheal permeability to DTPA and bronchoalveolar permeability to diethylenetriamine pentaacetate (DTPA) and bovine serum albumin (BSA) at 1 h after the exposure. Bronchoalveolar, but not tracheal, permeability remained elevated at 24 h after the exposure. Exercise during exposure to O3 increased permeability to both tracers in the tracheal and the bronchoalveolar zones, and prolonged the duration of increased permeability in the tracheal zone from 1 h to 24 h, and in the bronchoalveolar zone from 24 h to 48 h. Permeability in the tracheal and bronchoalveolar zones of rats exposed at rest to 6 or 12 ppm NO2 did not differ from controls. However, rats exposed during exercise to 12 ppm NO2 for 2 h developed a significant increase in tracheal and bronchoalveolar permeability to DTPA and BSA at 1 h, but not at 24 or 48 h, after exposure. Exposure at rest to 0.6 ppm O3 plus 2.5 ppm NO2 significantly increased bronchoalveolar permeability at 1 and 24 h after exposure, although exposure at rest to 0.6 ppm O3 alone increased bronchoalveolar permeability only at 1 h after exposure. Exposure to O3 + NO2 during exercise led to significantly greater permeability to DTPA than did exercising exposure to O3 alone. Resting rats exposed to a complex gas/aerosol atmosphere composed of the above O3 and NO2 concentrations, plus 5 ppm (13.1 mg/m3) sulfur dioxide (SO2) and an aerosol of insoluble colloidal Fe2O3 with an aerosol of manganese, ferric, and ammonium salts, demonstrated increased permeability at 1 and 24 h after exposure. Nitric acid vapor was formed in both the O3 + NO2 atmosphere and the complex gas/aerosol atmosphere.(ABSTRACT TRUNCATED AT 400 WORDS)     

The use of genomics technology to investigate gene expression changes in cultured human liver cells.

The field of genomics has great potential in toxicology; however, the technology is still in its infancy and there are many questions that need to be addressed. In this study we focus on the use of toxicogenomics for the determination of gene expression changes associated with hepatotoxicity. The human hepatoma cell line HepG2 was used to assess the toxic effects of two well-studied hepatotoxins, carbon tetrachloride (CCl(4)) and ethanol (EtOH). Replicate dishes of HepG2 cells were exposed to two concentrations of CCl(4) and EtOH--doses which caused 20% and 50% cell death (as determined by the MTT assay) were chosen [0.18% and 0.4% (v/v) CCl(4); 2.5% and 5% (v/v) EtOH] and the cells exposed for periods of 2 and 24 h. mRNA was extracted and used to probe Atlas Human Toxicology II arrays (Clontech). Preliminary data revealed that following a 2-h exposure at the low doses of both compounds, few changes in gene expression were detected. However, after 24-h exposure of the cells to the same low concentration of both compounds, multiple changes in gene expression were observed, many of which were specific to the individual hepatotoxins, presumably reflecting their different mechanisms of action. CCl(4) treatment of HepG2 cells gave rise to treatment specific up-regulation of genes involved in extracellular transport and cell signalling, whereas EtOH treatment gave rise predominantly to down-regulation of genes involved in stress response and metabolism. In addition, changes in regulation of certain genes (involved in stress response and cell cycle) were common to both treatments. Exposure of HepG2 cells to higher doses of the hepatotoxins gave rise to more changes in gene expression at lower exposure times. These results strongly suggest that different mechanisms of hepatotoxicity may be associated with specific patterns of gene expression, while some genes associated with common cellular responses may be useful as early markers of toxicity.     

Method for testing mutagenic effects of chemicals on spermatogonia of the Chinese hamster: results obtained with cyclophosphamide, saccharin, and cyclamate.

The action of different cyclophosphamide doses on spermatogonia of the Chinese hamster was examined. Two oral treatments at an interval of 24 h were carried out and spermatogonia were prepared for examination 24 or 48 h after the second dose. Accordingly the effects of 5 oral cyclophosphamide doses given on five consecutive days were tested on spermatogonia and preparations were made 24 or 72 h after the last treatment. The results so obtained form the basis of reference for findings following oral administration of saccharin sodium, sodium cyclamate, or trimethylphosphate. Male Chinese hamsters, 6-8 per group, were used, from each of which about 100 metaphases were evaluated. Preparation was carried out essentially according to Hoo and Bowles [Mutation Res. 13, 85-88 (1971)]. gaps, breaks, fragments, deletions and translocations were rated as structural aberrations. For every dose and every time of preparation the incidence of metaphases with aberrations, with or without gaps, and with translocations were assessed. The different experiments led to the following conclusions: 1. By analysis of spermatogonial metaphases of treated Chinese hamsters chemically induced chromosome aberrations can be proved with certainty. 2. Incidence of metaphases with translocations is a sensitive measure which is distinctly superior to the summary determination of all aberrations. In this way it was possible to show a mutagenic influence of 2 times 8 mg/kg cyclophosphamide p.o. 3. Following two cyclophosphamide doses administered at an interval of 24 h it was found that preparations of spermatogonia 48 h after the second dose was better suited for the evaluation than that at 24 h, for aberrations were more frequent with the same treatment. After five cyclophosphamide treatments at 24-h intervals, aberrations were somewhat more frequent 24 h after the last dose than at 72 h; in any case the values exceeded significantly the results of untreated controls. 4. A conclusive numeric chromosome analysis is not possible with the spermatogonia test, since a relatively high percentage of non-diploid cells is apparently of methodological origin. 5. Tests with 2 times 500 or 5 times 1000 mg/kg trimethylphosphate orally showed an increase in chromosome aberrations compared with controls indicating mutagenic effects in both cases; with 5 times 1000 mg/kg p.o., however, the figures were low as a result of marked mitotic inhibition. 6. The results of the spermatogonia test on Chinese hamsters revealed no mutagenic effects of saccharin sodium 2 times 5000 mg/kg orally, and of sodium cyclamate 5 times 2000 mg/kg orally. This is based on comparisons of the results both with untreated controls and positive controls treated with trimethylphosphate or cyclophosphamide.     

Dietary protection by iron against clastogenic effects of short-term exposure to arsenic in mice in vivo.

Iron, as freshly prepared aqueous solution of ferrous sulfate, was administered by gavage to laboratory bred Swiss albino mice. The concentration used was 152 mg/kg body weight (1/10 of the LD(50)). While screening for protection against arsenic, in one set of experiment exposure to iron was followed after 2 hr by gavaging with 2.5 mg/kg body weight (1/10 of the LD(50)) of arsenic as sodium (III) meta arsenite in distilled water. In another set, equal amounts (1:1) of ferrous sulfate and sodium arsenite were administered simultaneously. Control sets were given sodium m-arsenite alone and distilled water (vehicle). After exposure for 24 hr in all experiments, mice were sacrificed and chromosome preparations were made from bone marrow according to a colchicine-hypotonic-fixation-air-drying-Giemsa schedule. Cytogenetic endpoints screened were chromosome aberrations and divisional frequencies. Sodium arsenite alone was highly clastogenic. Ferrous sulfate, whether given together with or before exposure to sodium arsenite, reduced the clastogenic effects of the latter to a significant extent.     

The effect of age and exposure duration on cancer induction by a known carcinogen in rats,mice, and hamsters

Female Golden Syrian hamsters, F-344 rats, Swiss CD-1 mice, and B6C3F1 hybrid mice were exposed 6 hr/day, 5 days/week to carcinogenic levels of vinyl chloride (VC) for 6, 12, 18, or 24 months (rats and hamsters only). Other groups of rodents were held for 6 or 12 months and then exposed for 6 or 12 months. At the end of the study the incidence of VC-induced neoplasms was compared in each of the groups to assess the effects of duration of exposure and age at the start of exposure on carcinogenicity of VC. In rats, with early initial exposure, hemangiosarcomas, hepatocellular carcinomas, and mammary gland carcinomas occurred with increasing incidence with longer exposure duration. Rats held for 6 months before exposure developed VC-related neoplasms, while rats held 12 months before the start of exposure failed to show a significantly increased incidence of these neoplasms. In hamsters, hemangiosarcomas, mammary gland carcinomas, gastric adenocarcinomas, and skin carcinomas resulted from VC exposure. The highest incidence of malignant neoplasms occurred in hamsters exposed for the first 12 months, whereas exposure begun after 12 months of age did not cause neoplasms. In both strains of mice, VC exposure during the first 6 months of the experiment induced a high incidence of hemangiosarcomas and mammary gland carcinomas. Swiss mice also developed lung carcinomas after only 6 months of exposure. In all three rodent species an initial 12 month exposure to VC was adequate to detect its carcinogenic potential, but the shortened survival of VC exposed mice and hamsters precluded a meaningful comparison with longer periods of exposure. Exposures were most effective when started early in life.     

Antioxidant action of bixin against cisplatin-induced chromosome aberrations and lipid peroxidation in rats

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but has serious side effects, inducing nephrotoxicity and chromosome aberrations. In this study we evaluated the role of the carotenoid bixin on cisplatin-induced oxidative stress in Wistar rats through three markers of oxidative damage: chromosome aberrations, glutathione depletion and lipid peroxidation. The animals were divided into six treatment groups with six rats in each (n= 6). The dose of cisplatin (5.0 mg kg(-1)body wt.) was injected i.p. and bixin (2.5 or 5.0 mg kg(-1)body wt.) was given by gavage at 48, 24 h and 10 min before the cisplatin injection. The treatment with the highest dose of bixin resulted in a statistically significant reduction, by about 33%, in cisplatin-induced abnormal metaphases (P< 0.05). A single dose of cisplatin enhanced the formation of lipid peroxides in 29% and resulted in a 29% depletion in renal glutathione 24 h after cisplatin administration (P< 0.05). The pretreatment with bixin reduced the total number of chromosome aberrations, inhibited the increase in lipid peroxidation, and inhibited renal glutathione depletion induced by cisplatin. Since the pretreatment with bixin alone was safe, under the present experimental conditions, the results suggest that bixin may have future clinical application after further studies.     

In vitro investigation of the genotoxic and cytotoxic effects of thiacloprid in cultured human peripheral blood lymphocytes

Thiacloprid, a neonicotinoid insecticide, is widely used for controlling various species of pests on many crops. The potential genotoxic effects of thiacloprid on human peripheral blood lymphocytes (PBLs) were investigated in vitro by the chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and cytokinesis‐block micronucleus (MN) assays. The human PBLs were treated with 75, 150, and 300 μg/mL thiacloprid in the absence and presence of an exogenous metabolic activator (S9 mix). Thiacloprid increased the CAs and SCEs significantly at all concentrations (75, 150, and 300 μg/mL) both in the absence and presence of the S9 mix and induced a significant increase in MN and nucleoplasmic bridge formations at all concentrations for 24 h and at 75 and 150 μg/mL for 48‐h treatment periods in the absence of the S9 mix; and at all concentrations in the presence of the S9 mix when compared with the control and solvent control. Thiacloprid was also found to significantly induce nuclear bud (NBUD) formation at 300 μg/mL for 24 h and at 150 μg/mL for 48‐h treatment times in the absence of the S9 mix and at the two highest concentrations (150 and 300 μg/mL) in the presence of the S9 mix. Thiacloprid significantly decreased the mitotic index, proliferation index, and nuclear division index for all concentrations both in the absence and presence of the S9 mix. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 631–641, 2014.     

Effects of natamycin on sister chromatid exchanges,chromosome aberrations and micronucleus in human lymphocytes

Natamycin (pimaricin) (E235) is an antifungal that can be used as an antibiotic to treat most fungus infections. It has been globally used in a variety of foods and beverages. In the present study, the effects of natamycin on chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) formation in human lymphocytes cells were investigated. The human lymphocytes were treated with 13, 18, 23, and 28 μg/mL of natamycin for 24 and 48 h. Natamycin induced the SCE frequency at the highest concentration for 48 h only; however, it induced the structural CA and MN frequency at all concentrations when compared to control and at all concentrations, except the lowest concentration (13 μg/mL), when compared to solvent control. Natamycin showed a cytotoxic effect by decreasing the replication index, mitotic index, and nuclear division index (NDI), especially at the highest concentrations for two treatment periods.     

Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms

The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increase of genetic damage (p<0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.