Application of the micronucleus test to exfoliated epithelial cells from the oral cavity of beedi smokers, a high-risk group for oral cancer.

The primary sites for occurrence of oral cancer include the buccal mucosa, tongue, alveolus, palate, lip and the floor of the mouth. In this study, an attempt was made to estimate the cytogenetic damage in different regions of the oral mucosa in people habituated to smoking beedi,which is one of the major forms of tobacco consumption in India and believed to be a major risk factor for oral cancer. By using the micronucleus assay on exfoliated cells from the buccal mucosa, palate and tongue of beedi smokers, we examined an early cellular response to the effect of beedi smoking. A total number of 50 randomly selected male subjects were included in the study. Case and control groups (smokers and non-smokers, respectively) comprised 25 subjects each. The difference in mean micronucleated cell count between cases and controls was significant (P <0.01) for buccal mucosa and palate, but not for tongue. The correlation between age and micronucleus cell count was weak for both cases (r=0.27) and controls (r=0.36).

Comparative evaluation of background micronucleus frequencies in domestic mammals.

Exposure of human alimentation-destined animals to toxic substances can be an important risk factor for human health. Mutagenicity tests represent a good method for genotoxic effect evaluation of environmental pollutants. The micronucleus frequency in peripheral blood and bone marrow erythrocytes has been evaluated in four domestic Ungulate species (ox, sheep, swine and horse). For each species two or three groups of animals coming from Italy and other European countries were analysed and the results indicate a relatively low mean frequency of micronucleated erythrocytes (ME), both in peripheral blood and bone marrow. The comparison between these two frequencies in the four species studied shows that the ME frequency in sheep and horse is significantly higher in peripheral blood than in bone marrow, whereas in bovines it is higher in the bone marrow, and in swine the difference is not significant. These results could indicate that in ox and swine the spleen is involved in ME removal from the peripheral circulation, as is known for other species including man. Nevertheless, it cannot be excluded that the same occurs in the other two species, since they exhibit a relatively low peripheral blood ME frequency as well. Further studies on domestic mammals are needed to clarify the spleen function and verify the use of the peripheral blood micronucleus test for genotoxic biomonitoring. At present, the application of the micronucleus test to the bone marrow seems a more suitable method, but, being invasive, it can be used only as a control system of animal hygiene and health, in addition to the routine tests, rather than for biomonitoring.

Actividad genotóxica de la terapia con I131 en pacientes tratados por carcinomas de tiroides / Genotoxic activity of the I 131 therapy in patients treated for thyroid carcinoma

- Introducción: El test de micronúcleos (MN) sobre linfocitos humanos irradiados con bloqueo citocinético (CB) se utiliza para valorar el daño cromosómico y genotóxico de diferentes agentes físicos y químicos.- Objetivo: Determinar un posible efecto genotóxico inducido por la terapia con I131 en pacientes con cáncer de tiroides y determinar la dosis equivalente corporal total (DECT) de radiación ionizante que supone dicho tratamiento.- Material y métodos: Se ha determinado la frecuencia de aparición de MN en cultivos de linfocitos CB en tres grupos de individuos diferentes: 1) en 35 voluntarios sanos para establecer la frecuencia espontánea de MN; 2) en 9 voluntarios supuestamente sanos para realizar las curvas dosisrespuesta "in vitro" con radiación gamma; y 3) en 25 pacientes que han recibido una dosis ablativa de I131 en el tratamiento de un carcinoma de tiroides. Se ha determinado el número de MN/500 células CB previo al tratamiento y tres días después de la administración de I131. La DECT de la terapia se ha calculado por el número de MN en linfocitos obtenido a los tres días de la administración de I131 comparada con la frecuencia de MN expuestas "in vitro" a radiación gamma que produciría una idéntica frecuencia de MN.- Resultados: Se ha obtenido una relación lineal entre la frecuencia de MN y la dosis de radiación ionizante administradas "in vitro" con radiación gamma. La frecuencia de MN tras el tratamiento con I131(8´89 MN/500CB) es significativamente mayor (p<0.01), duplicando la frecuencia espontánea (4´08/500MN) basal.- Conclusión: La terapia con I131 induce un incremento significativo del daño cromosómico en los pacientes irradiados por carcinoma de tiroides, equivalente a una dosis corporal total de 13 cGy durante los tres primeros días desde la administración terapéutica de I131 (AU)

Low dose induction of micronuclei by lindane.

Environmental contaminants possessing hormonal activity have long been suspected of playing a role in cancer causation. What is unclear is whether such agents elicit their effects through genotoxic and/or epigenetic mechanisms. gamma-Hexachlorocyclohexane (gamma-HCH, lindane) was tested in the 10(-12)-10(-4) M range. Chromosomal damage in MCF-7 breast cells and PC-3 prostate cells was assessed using the cytokinesis block micronucleus assay. Micronuclei (MNi) were scored in 1000 binucleate cells per treatment. Cell viability and cell cycle kinetics were also assessed, along with immunocytochemical and quantitative gene expression analyses of CDKN1A (P21WAF1/CIP1), BCL-2 and BAX. Following 24 h treatment, lindane (10(-12)-10(-10) M) induced increases (up to 5-fold) in MNi in both cell lines. Increases in MNi occurred in the absence of DNA single-strand breaks or cytotoxicity and, compared with benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, at low concentrations. Lindane induced more MNi than the alpha or beta stereoisomers of HCH. Low dose lindane (10(-12)-10(-10) M) significantly elevated the percentage of MCF-7 cells staining positive for Bcl-2 and of PC-3 cells staining positive for Bax. Only high dose lindane (10(-4) M) disrupted cell cycle kinetics with increases in percentage of cells in G1 and decreases in percentage of cells in G2/M. Despite a comparable high dose lindane induction of cell cycle arrest, marked increases in expression of P21WAF1/CIP1 were observed only in MCF-7 cells, although in PC-3 cells a significant increase (P < 0.0005) in the percentage of cells staining positive for p21Waf1/Cip1 was seen. These results suggest that 'environmental' concentrations of lindane can induce a number of subtle alterations in breast and prostate cells in the absence of cytotoxicity.

An assessment of the genotoxicity of 2-hydroxy-1,4-naphthoquinone, the natural dye ingredient of Henna.

2-Hydroxy-1,4-naphthoquinone (HNQ; Lawsone; CAS 83-72-7) is the principal natural dye ingredient contained in the leaves of Henna (Lawsonia inermis). Published genotoxicity studies on HNQ suggested it was a weak bacterial mutagen for Salmonella typhimurium strain TA98 or was more clearly mutagenic for strain TA 2637, both in the presence of metabolic activation. HNQ was unable to induce sex-linked recessive lethal mutations in Drosophila melanogaster. However, a small increase in micronucleus frequency was reported in the bone marrow of mice at a single mid-range dose level, 24h after intraperitoneal injection. In view of the wide use of Henna hair dyes it was deemed necessary to conduct a thorough investigation, under Good Laboratory Practice conditions, of the genotoxicity of HNQ. HNQ was non-mutagenic in bacterial (Ames test) or mammalian (V79 hprt) assays. It was borderline positive in a mouse lymphoma tk mutation assay and a chromosome aberration test (CHO cells), results that may reflect a similar clastogenic mechanism. Negative in vivo genotoxicity results were noted in the rat hepatocyte in vivo/in vitro UDS test, in peripheral lymphocytes (chromosome aberrations) of rats receiving repeated oral doses of HNQ at the MTD for 28 days, and in mouse and hamster bone marrow chromosome aberration tests. However small, but statistically significant increases in the incidence of bone marrow micronuclei were observed in two out of five tests at 72 h after dosing, but not at 24 or 48 h. There was evidence of haematotoxicity at 72 h, which may have been enhanced by the vehicle (DMSO) used in the positive tests. As erythropoiesis and administration of haematotoxic agents are known to induce small increases in the frequency of bone marrow micronuclei, typically at delayed sampling times, the data suggest that the positive 72 h response produced by HNQ is consistent with stimulation of haematopoiesis subsequent to haematological toxicity of HNQ, and not due to a DNA-reactive mechanism. Overall, the weight of evidence suggests that Henna and HNQ pose no genotoxic risk to the consumer.

Preimplantation mouse embryo development as a target of the pesticide methoxychlor.

Effects of methoxychlor (MXC) and estradiol-17beta (E) were studied in mouse preimplantation embryos. Pregnant mice received s.c. injections of sesame oil only, 10 microg E, or 0.5 mg purified (95%) MXC on Days 2-4 of pregnancy (plug = Day 1). Another group received a single dose of 2.5 microg E on Day 2 only. Based on the average weight of pregnant females, 10 microg of estradiol was equivalent to 0.33 mg/kg of bw, 2.5 microg of estradiol was equivalent to 0.082 mg/kg of bw, and the 0.5-mg dose of MXC was equivalent to 16.5 mg/kg of bw. All embryos were collected for analyses on Day 4. MXC and both estradiol-17beta doses suppressed embryonic development to blastocyst, decreased embryo cell numbers, and caused abnormal blastocyst formation. The high estradiol-17beta dose significantly increased the percent degenerating embryos and caused a tube-locking effect, with retention of embryos in the oviduct. In contrast to estradiol-17beta, MXC at the dose used in this study did not alter tubal transport of embryos. Also in contrast to estradiol-17beta, MXC increased the percentage of nuclear fragmentation and micronuclei. In preimplantation embryos, MXC and estradiol-17beta both suppressed embryo development. MXC effects were, however, different from those of estradiol-17beta, indicating a difference in mechanism of action, possibly due to cytotoxicity and induction of apoptosis.

[Cytogenetic changes of the bone marrow in massive blood loss and their correction with mexidol]. / Tsitogeneticheskie izmeneniia kostnogo mozga pri massivnoi krovopotere i ikh korrektsiia meksidolom.

The citogenetic lesions were evaluated in the marrow erythroblasts of 45 anesthetized white nonlinear male rats, weight--200-300 g who were subjected to an acute blood loss with a 1-hour arterial hypotension (ABR = 40 mm Hg); the micronucleus tests was made use of. Two stages of the increase of polychromatophilic erythrocytes with micronuclei in the marrow of the animals, who underwent a massive blood loss, were registered: stage 1--an incomplete marrow ischemia with a subsequent arterial hypotension and with a reliably confirmed formation of cytogenetic lesions in the marrow polychromatophilic erythrocytes; stage 2--the reperfusion period contributed to a 1.7-fold increase of polychromatophilic erythrocytes with micronuclei versus the previous stage. Mexidole, when used at 50 mg/kg prior to blood reinfusion, decreased the quantity of polychromatophilic erythrocytes with micronuclei to the basic level, which is indicative of reversibility and instability of cytogenetics impairments in the marrow cells of animals observed in the early post-resuscitation period.

Effects of a diet high in fish oil (MaxEPA) on the formation of micronucleated erythrocytes in blood and on the number of atypical acinar cell foci Induced in rat pancreas by azaserine.

The present study was performed to investigate the influence of fish oil on the genotoxic effects of azaserine, using the formation of micronucleated erythrocytes as a measure for the degree of initiating potency and the number and size of putative preneoplastic pancreatic atypical acinar cell foci (AACF) as a measure for the actual number of initiated cells. Male Wistar rats were treated twice i.p. with 30 mg azaserine per kg body weight to induce AACF. During the initiation/early promotion phase the rats were maintained on diets containing 5 wt% vegetable oil (safflower and high-oleic sunflower oil), 25 wt% vegetable oil, 25 wt% fat (15% vegetable oil + 10 wt% fish oil), or 25 wt% fat (5% vegetable oil + 20 wt% fish oil), respectively. One day after carcinogen treatment, the numbers of micronucleated polychromatic erythrocytes were determined in blood smears obtained from 10 animals per group. Each high-fat diet resulted in higher percentages of micronucleated polychromatic erythrocytes than the low-fat diet. Dietary fish oil did not significantly influence the number of micronucleated cells. Two weeks after carcinogen treatment, the diets containing fish oil were replaced by the diet containing 25% vegetable oil, and the animals were further maintained for about 14 wk. Pancreatic tissue slides were microscopically evaluated for the number and size of AACF. Dietary fish oil caused an increase in the number and size of AACF, although a clear dose-effect relationship was absent. It was concluded that a high level of dietary fish oil, when given during the induction/early promotion phase, enhances azaserine-induced pancreatic carcinogenesis in rats.

Inhibitory effect of chlorophyllin on the frequency of micronuclei induced by sodium nitrite in mice.

In this report the potency of chlorophyllin (CHL) was evaluated to prevent two types of damage produced by nitrite in mice: the increase of micronucleated polychromatic erythrocytes (MNPE) and the bone marrow toxicity, measured as the index of polychromatic erythrocytes/normochromatic erythrocytes (PE/NE). The study was done in eight groups of male mice. The first three groups were administered orally for 4 days with sodium nitrite (10, 15 and 20 mg/kg), the daily administration with nitrite was followed by an intraperitoneal administration of CHL (4 mg/kg), three more groups were administered with the same amounts of nitrite, a seventh group of mice was treated with distilled water while another was treated with CHL (4 mg/kg). Our study produced two main results: (a) no bone marrow injury was induced by any of the tested chemicals, as indicated with the PE/NE index, and (b) CHL protected (as high as 44%) the MNPE produced in nitrite treated mice.

Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells.

The dietary phytochemical curcumin possesses anti-inflammatory, -oxidant, and cytostatic properties, and exhibits significant potential as a chemopreventative agent in humans. Although many cell types are arrested in the G2/M-phase of the cell cycle after curcumin treatment, the mechanisms by which this occurs are not well understood. The purpose of this study was to examine the effects of curcumin on the cell cycle of MCF-7 breast cancer cells to determine whether growth arrest is associated with structural changes in cellular organization during mitosis. For this purpose, MCF-7 breast cancer cells were treated with 10-20 microM curcumin, and the effects on cell proliferation and mitosis studied. Structural changes were monitored by immunolabeling cells with antibodies to a number of cytoplasmic and nuclear proteins, including beta-tubulin, NuMA, lamins A/C and B1, lamin B receptor, and centromere antigens. At the concentrations used, a single dose of curcumin does not induce significant apoptosis, but is highly effective in inhibiting cell proliferation for over 6 days. During the first 24-48 h of treatment, many cells are arrested in M-phase, and DNA synthesis is almost completely inhibited. Remarkably, arrested mitotic cells exhibit monopolar spindles, and chromosomes do not undergo normal anaphase movements. After 48 h, most cells eventually leave M-phase, and many form multiple micronuclei instead of individual daughter nuclei. These observations indicate that the curcumin-induced G2/M arrest previously described for MCF-7 cells is due to the assembly of aberrant, monopolar mitotic spindles that are impaired in their ability to segregate chromosomes. The production of cells with extensive micronucleation after curcumin treatment suggests that at least some of the cytostatic effects of this phytochemical are due to its ability to disrupt normal mitosis, and raises the possibility that curcumin may promote genetic instability under some circumstances.

Persistence of micronuclei in lymphocytes of cancer patients after radiotherapy.

To verify the applicability of the micronucleus (MN) yield in peripheral blood lymphocytes (PBLs) as a quantitative biodosimeter for monitoring in vivo ionizing radiation damage, we applied the cytokinesis-blocked micronucleus assay in PBLs of cancer patients treated with partial-body radiotherapy. Dosimetric information on these 13 patients represented a wide range in the number of fractions, cumulative tumor dose, total integral dose, and equivalent total-body absorbed dose. We found in PBLs of these patients that (1) the MN yield increased linearly with the equivalent total-body absorbed dose (r = 0.8, P = 0.002), (2) the distributions of the MN yields deviated significantly from Poisson, and (3) there was a general decline in MN yields with increasing length of follow-up, but with considerable variation between individuals. The average rate of decline was found to be linear and was correlated with the equivalent total-body absorbed dose (r = 0.7, P = 0.007). Further, at 19-75 months of follow-up time, seven patients showed higher MN yields than their respective levels before radiotherapy, indicating the persistence of radiation-induced residual cytogenetic damage. Our findings suggest that the MN yield in human PBLs offers a reliable acute and perhaps chronic biodosimeter for in vivo radiation dose estimation. After the completion of radiotherapy, the persistence of elevated MN yield in PBLs is a reflection of the surviving population of radiation-induced genetically aberrant cells.

Enhanced frequency of micronuclei in individuals exposed to arsenic through drinking water in West Bengal, India.

In West Bengal, India arsenic in ground water has been found to be above the maximum permissible limit in seven districts covering an area of 37,493km2. In the present study, evaluation of the micronuclei (MN) formation in oral mucosa cells, urothelial cells and peripheral blood lymphocytes was carried out in the symptomatic individuals exposed to arsenic through drinking water. Forty five individuals with cutaneous signs of arsenicism from four affected districts (368.11 microg/l of As in drinking water) were considered as the exposed group and 21 healthy individuals with no symptoms of arsenic poisoning and residing in two unaffected districts (5.49 microg/l of As) were considered as controls. The exposed and control groups had similar age distribution and socioeconomic status. Standardised questionnaires were utilised and medical examination was conducted to ascertain exposure history, sociodemographic characteristics, diet, health, medication, addiction and chief symptoms in the study participants. Arsenic exposure was confirmed by measuring the arsenic content in the drinking water, nails, hair and urine samples from the volunteers. Arsenic contents in the urine, nail and hair in the exposed group were 24.45 microg/l, 12.58 and 6.97 microg/g, respectively which were significantly high in comparison to corresponding control group values of 4.88 microg/l, 0.51 and 0.34 microg/g, respectively. Exposed individuals showed a statistically significant increase in the frequency of MN in oral mucosa, urothelial cells and lymphocytes (5.15, 5.74 and 6.39/1000 cells, respectively) when compared with the controls (0.77, 0.56 and 0.53/1000 cells, respectively). Thus, the above results indicate that the symptomatic individuals exposed to arsenic through drinking water in this region have significant cytogenetic damage.

Micronuclei in cervical smears and peripheral blood lymphocytes from women with and without cervical uterine cancer.

Cervical cancer represents the second most common malignant neoplasia in women world-wide. In Mexico, cervical cancer is the most common female malignancy. It has been recently seen an increased frequencies of micronuclei (MN) lymphocytes and cervical epithelial cells of cervical cancer patients. The aim of this hospital-based unmatched case-control study was to investigate the association between progressive stages in development of cervical cancer and frequency of micronucleated cells in the cervical epithelium and peripheral lymphocytes of 40 women, grouped by disease stage. Women at the Obstetrics and Gynecology Hospital of the Instituto Mexicano del Seguro Social (IMSS) in Monterrey, Mexico were diagnosed and classified on the bases of the Papanicolaou (PAP) smear and colposcopy/biopsy into control, low-grade squamous intraepithelial lesions (LGSIL), high-grade squamous intraepithelial lesions (HGSIL), and invasive groups. Analysis of the MN data in both cell types revealed (a) homogeneity among women within each of the four groups with regard to MN frequency, (b) in general, a correlation between MN frequency and grade of cervical lesion, and (c) a positive linear trend between the MN frequency and increased cervical cancer risk. In conclusion, we suggest that MN are a useful biomarker of cancer risk. Nonetheless, these results should be validated by other researchers.

Cytogenetic alterations in lymphocytes of Alzheimer's disease and Parkinson's disease patients.

We investigated the presence of cytogenetic alterations in peripheral blood lymphocytes of Alzheimer's disease (AD) and Parkinson's disease (PD) patients. Detection of spontaneous structural and/or numerical chromosome damage has been assessed by micronucleus (MN) assay coupled with fluorescence in situ hybridization (FISH). The cytogenetic investigation was performed on 22 AD patients, 18 PD patients, and 20 controls. The spontaneous frequencies of micronuclei (MN) in human lymphocytes of both AD and PD patients were significantly higher than in controls. The majority of MN was composed of whole chromosomes in AD patients, while a prevalence of MN arising from chromosome breakage was observed in PD patients. Different molecular mechanisms underlie cytogenetic alterations observed in peripheral lymphocytes of AD and PD patients.

Association of HSP70 and genotoxic damage in lymphocytes of workers exposed to coke-oven emission.

Heat shock proteins (Hsps) have been reported to protect cells, tissues, and organisms against damage from a wide variety of stressful stimuli. Whether they protect against deoxyribonucleic acid (DNA) damage in individuals exposed to environmental stresses and chemical carcinogens is unknown. In the study, we investigated the association between Hsp70 levels (the most abundant mammalian Hsp) and genotoxic damage in lymphocytes of workers exposed to coke-oven emission using Western dot blot and 2 DNA damage assays, the comet assay and the micronucleus test. The data show that there is a significant increase in Hsp70 levels, DNA damage score, and micronucleus rates in lymphocytes of workers exposed to coke-oven emission as compared with the control subjects. Furthermore, there was a significant negative correlation of Hsp70 levels with DNA damage scores in the comet assay (r = -0.663, P < 0.01) and with micronucleus rates (r = -0.461, P < 0.01) in the exposed group. In the control group, there was also a light negative correlation between Hsp70 with DNA damage and micronuclei rate (r = -0.236 and r = 0.242, respectively), but it did not reach a statistically significant level (P > 0.05). Our results show that individuals who had high Hsp70 levels generally showed lower genotoxic damage than others. These results suggest a role of Hsp70 in the protection of DNA from genotoxic damage induced by coke-oven emission.

A unifying model for reconstructing radiosensitivity from micronucleus formation, apoptosis and abnormal morphology.

At present micronucleus data cannot predict cellular radiosensitivity. The inclusion of data from apoptosis and abnormal morphology has not entirely resolved this problem. Here, we assess the probability of cell death arising from events other than micronucleation, apoptosis and abnormal morphology (i.e. lesions not detected by these damage assays) P(oe), for its ability to reflect intrinsic cellular radiosensitivity. Analysis of data from 17 cell lines used in two separate studies, spanning a wide range of radiosensitivity (0.09

Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in inner Mongolia, China.

The groundwater in Bayingnormen (Ba Men), located in Central West Inner Mongolia, China, is naturally contaminated with arsenic at concentrations ranging from 50 microg/L to 1.8 mg/L. Various adverse health effects in this region, including cancer, have been linked to arsenic exposure via drinking water. A pilot study was undertaken to evaluate frequencies of micronuclei (MN), as measures of chromosomal alterations, in multiple exfoliated epithelial cell types from residents of Ba Men chronically exposed to arsenic via drinking water. Buccal mucosal cells, airway epithelial cells in sputum, and bladder urothelial cells were collected from 19 residents exposed to high levels of arsenic in drinking water (527.5 +/- 24 microg/l), and from 13 control residents exposed to relatively low levels of arsenic in drinking water (4.4 +/- microg/L). Analytical results from these individuals revealed that MN frequencies in the high-exposure group were significantly elevated to 3.4-fold over control levels for buccal and sputum cells, and to 2.7-fold over control for bladder cells (increases in MN frequency significant at p < .001 for buccal cells; p < .01 for sputum cells; p < .05 for bladder cells). When smokers were excluded from high-exposure and control groups the effects of arsenic were observed to be greater, although only in buccal and sputum cells; approximately 6-fold increases in MN frequency occurred in these tissues. The results indicate that residents of Ba Men chronically exposed to high levels of arsenic in drinking water reveal evidence of genotoxicity in multiple epithelial cell types; higher levels of induced MN were observed in buccal and sputum cells than in bladder cells.

Sex chromosome loss, micronuclei, sister chromatid exchange and aging: a study including 16 centenarians.

In the present study we analysed the possible effect of age, sex and smoking on the mean values of micronucleus (MN) and sister chromatid exchange (SCE) frequencies on peripheral blood obtained from 38 subjects ranging in age from 16 to 63 years and 16 centenarians. The mean number of binucleated cells with micronuclei varied in function of age and sex (as demonstrated by the analysis of covariance (F=13.13; P<0.001), particularly evident was the increment observed in women with increasing age (interaction age/sex: F=5.53; P<0.05). Smoking habits had no effects on MN frequency (F=0.36; P>0.05). Sex (F=4.18; P<0.05) and smoking habits (F=14.64; P<0.001) influenced significantly SCE per cell frequencies, but age had no effects on them (F=2.45; P>0.05). The age-associated increase of sex chromosome loss was studied using fluorescence in situ hybridisation (FISH) on interphase nuclei. The loss of Y signals was observed in approximately 10% of interphase cells from the centenarians males, that is six times more often than in the younger control men (approximately 1.6%). The frequency of X signal loss (approximately 1.7%) in young women was similar to that observed in male controls of the same age but the incidence of the X chromosome aneuploidy in centenarian females was appreciably higher (approximately 22%) than that found for the Y chromosome in males. These results were correlated with the data on MN formation and a positive correlation between the percentage of aneuploid cells (FISH) and MN values was observed (r=0.50; P<0.05).

[Comparative study of the effect of synthetic pyrethroids on the induction of genetic changes in mice somatic and sex cells depending on the exposure route]. / Porównawcze badania wplywu syntetycznych pyretroidów na indukcje zmian genetycznych w komórkach somatycznych i plciowych myszy w zaleznosci od drogi narazenia.

Synthetic pyrethroid insecticides are widely used in the protection of fruits and vegetables as well as in the public hygiene due to their strong neurotoxic activity against insects. The induction of genetic changes in somatic and sex cells in male mice after different routes of exposure to permethrin and fenvalerate was studied. The male 8-10 weeks old mice were intraperitoneally exposed to 20 and 40 mg/kg bw of fenvalerate and 125 and 250 mg/kg bw of permethrin. Another groups of mice were exposed per os to fenvalerate and permethrin in the doses of 50, 100 and 200, 400 mg/kg bw respectively. For the sperm anomalies testing the exposure was repeated for five consecutive days followed by the 35 days waiting period after which the gonads were removed and spermatozoa prepared from the epididymis. The changed spermatozoa were counted in the smears after staining in the 0.5% eosin Y solution and the results compared with the number of normal cells. For the testing of the effect of pyrethroids on the micronuclei frequency in the bone marrow cells the tested substances were administered twice in 24 hours intervals and the bone marrow was sampled after 6 and 24 hours from the femur bone. The polychromatic erythrocytes and the presence of micronuclei were evaluated in the bone marrow smears. The results showed the difference in the action of the pyrethroids on the genetic material of the tested cells and the effect of the route of exposure. Permethrin induced the lesions in the sex cells regardless the route of exposure, however a substantial increase in the micronuclei frequency in the bone marrow was observed after oral exposure only. No signs of cytotoxicity accompanied the sperm anomalies and micronuclei induction. Fenvalerate induced changes in sperm cells after intraperitoneal exposure only. No increase in the micronuclei frequency in the polychromatic erythrocytes of the bone marrow was observed after per os or intraperitoneal exposure. The intraperitoneal exposure to this pyrethroid resulted in cytotoxicity in both bone marrow and sex cells.