Bioinformatics approaches to the study of antimicrobial resistance.

Detection and monitoring of antimicrobial resistance are two pillars on which clinical microbiology will be based in the coming decades. The implementation of certain technologies such as whole genome sequencing (WGS) or mass spectrometry and the creation of national and international databases that include and gather data on antimicrobial resistance from around the world has allowed the application of bioinformatics in the study of antimicrobial resistance in microorganisms involved in human pathology.

Variation among endoscopy units in the achievement of the standards of colonoscopic performance indicators.

BACKGROUND/AIMS: To assess the achievement of quality standards of colonoscopy at six endoscopy units. METHODOLOGY: Three indicators were used to assess the quality of 1056 colonoscopies performed at six hospitals: cecal intubation; adequate colon cleansing; and removal and recovery of all detected polyps. Analyses were performed on the total number of colonoscopies and on colonoscopies in which polyps were actually detected. The accomplishment of each indicator and a global compound index of all three indicators, named the Problem Rate, were analyzed. Results from each endoscopy unit were compared to previously established standards. RESULTS: Adequate colon cleansing was the most frequent problem for quality in all centers; adequate colon preparation was 67% (range 50 to 84%). The cecum was reached in 84% of all colonoscopies (range 76 to 90%). 75% of all patients (range 28. 79%) had all polyps excised and recovered. All centers had rates below standard for one or several indicators (p<0.01, all cases). Two of the participant hospitals had an overall problem rate above the estimated standard (p<0.01). CONCLUSIONS: There is a significant variation in the achievement of quality standards of colonoscopy between endoscopy units. Colon cleansing is the most frequent quality problem for colonoscopy.

Clinical impact of rapid molecular detection of respiratory pathogens in patients with acute respiratory infection.

BACKGROUND: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality worldwide. There is a need to demonstrate the clinical impact of using the new, rapid and sensitive molecular assays in prospectively designed studies. OBJECTIVES: To study the impact on medical management of a rapid molecular assay in patients with respiratory infections. STUDY DESIGN: A prospective, randomized, non-blinded study was performed in patients presenting to the Emergency Department during two respiratory seasons (2016-2017). Diagnosis was performed by FilmArray Respiratory Panel (FilmArray-RP) or by immunofluorescence assay (IFA). RESULTS: A total of 432 patients (156 children and 276 adults) were analyzed. Diagnosis with FilmArray-RP was associated with significant changes in medical management including withholding antibiotic prescriptions (OR:15.52, 95%CI:1.99-120.83 in adults and OR:12.23, 95%CI:1.56-96.09 in children), and reduction in complementary studies in children (OR:9.64, 95%CI:2.13-43.63) compared to IFA. Decrease in oseltamivir prescriptions was significantly higher in adults in the FilmArray-RP group (p = 0.042; OR:1.19, 95%CI:0.51-2.79) compared to adults managed with IFA. Diagnostic yield was significantly higher by FilmArray-RP (81%) than by IFA (31%)(p < 0.001). The median time from sample collection to reporting was 1 h 52 min by FilmArray-RP and 26 h by IFA (p < 0.001). CONCLUSIONS: The high respiratory viruses' detection rate and availability of results within two hours when using FilmArray-RP were associated with decreases in antibiotic prescriptions and complementary studies and more accurate use of oseltamivir.

Genetic instability induced by low doses of x-rays in hamster cells.

PURPOSE: Genomic instability involves time delayed events and can be manifested as elevated rates of heritable changes in the progeny of irradiated cells. To study the induction of chromosomal instability by very low doses of radiation Chinese Hamster Ovary (CHO) cells were exposed to 10-50 milisieverts (mSv) (approximately 10-50 miligrays (mGy)) of x-rays. MATERIALS AND METHODS: Control and irradiated cell populations were assayed for chromosomal aberrations and assessed using a micronucleus test and anaphase-telophase analysis at the first cell division post-irradiation and at every four population doublings thereafter up to 16 population doublings post-irradiation. RESULTS: Frequencies of micronuclei, anaphase-telophase alterations and chromosomal aberrations were increased when the cells were analysed immediately after x-ray exposure. Micronuclei and anaphase-telophase alterations showed significantly increased frequencies when they were analysed at 12 and 16 population doublings after exposure to 50 mSv. Chromosomal aberrations increased significantly at 12 and 16 population doublings after exposure to 10 mSv and 50 mSv. CONCLUSIONS: Our results are consistent with the presence of a phenomenon by which the initial DNA damage in the surviving cells is memorized. Micronuclei and achromatic lessions were the main cytogenetic damage observed in cells exposed to very low doses of x-rays, indicating that these low doses are able to induce genetic instability.

Applicability of the Rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding.

BACKGROUND: The Rockall score is used to assess the prognosis of patients with upper gastrointestinal bleeding. AIM: To assess the applicability of the Rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding. METHODS: Retrospective evaluation of the Rockall score in the period 1995-2001. To evaluate the applicability of the Rockall system, two groups were created: group I (Rockallor=6 points). RESULTS: Two hundred and twenty-two patients were included. The median age of patients was 65 +/ -17 years. Hypotension and associated diseases were present in 20 and 50% of patients, respectively. Re-bleeding occurred in 50 patients (23%) whose median score was 7, whereas the median score of patients without re-bleeding was 6 (p=0.14). There were 20 deaths (9%) with a median score of 8, whilst the median score of surviving patients was 6 (p<0.001). Sixteen patients in group I (18.4%) and 34 in group II (25.2%) re-bled (p=0.25). All the patients who died belong to group II with a Rockall score>or=6 (15% versus 0% in groups II and I, respectively, p<0.001). CONCLUSION: The Rockall score can be used in patients who undergo therapeutic endoscopy for upper gastrointestinal bleeding to identify those with high risk for mortality.

Folic acid enhances the apoptotic and genotoxic activity of carboplatin in HeLa cell line.

In human tumor cells, experimental and clinical evidence indicates that some factors involved in signal transduction and cell growth can also modulate the response to chemotherapeutic treatment. The aim of the present study was to investigate the role of folic acid (FA) as a modulator of carboplatin (CBDCA) activity. Genotoxicity and cytotoxicity induced by CBDCA alone and in combination with FA were assessed in cultured HeLa cells. We used comet assay, mitotic index analysis, MTT and NR assays, cytokinesis-block micronucleus cytome assay and annexin V-IP as different cytotoxicity and genotoxicity approaches for human cervical carcinoma cell line studies. The results showed that addition of 900nM FA together with 40.4mM CBDCA enhanced the activity of the platinum compound, increasing its effect on cell death by nearly 20%, as evidenced by the MTT and NR assays. Moreover, not only higher levels of DNA and chromosomal damage were reached but also the number of necrotic and apoptotic cells were significantly increased when cell cultures were treated with the combined procedure. This situation opens the possibility to explore the use of FA in platinum-based chemotherapy protocols to reduce the platinum doses for patient treatment and decrease the chance of developing the known side effects without losing biological activity.

A comparative study of the target volume definition in radiotherapy with «Slow CT Scan¼ vs. 4D PET/CT Scan in early stages non-small cell lung cancer. / Estudio comparativo en la definición del volumen de tratamiento en radioterapia con «Slow TC Scan¼ vs. 4D PET/TC Scan en estadios iniciales de cáncer de pulmón de célula no pequeña.

OBJECTIVES: To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow¼-CT (CTs) in the radiotherapy planning process. MATERIAL AND METHODS: A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. RESULTS: The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. CONCLUSION: Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer.

Nonpolar interactions in the maleimide inactivation of Haemophilus influenzae D-lactate dehydrogenase.

A series of N-alkylmaleimides varying in chain length from N-ethyl up to and including N-heptyl, was shown to effectively inactivate Haemophilus influenzae D-lactate dehydrogenase at pH 7.0 and 25 degrees C in processes proposed to involve covalent modification of cysteine residues. The inactivation proceeded through an initial reversible binding of maleimides facilitated by nonpolar interactions with a hydrophobic region of the enzyme. Subsequent irreversible inactivation of the enzyme indicated the modification of a fast-reacting group leading to approx. 80% loss of enzyme activity followed by a second slower-reacting modification process. At saturating concentrations of maleimides, the second inactivation process exhibited a common pseudo-first-order rate constant of 0.6 min-1. The initial reversible binding of N-alkylmaleimides resulted in inhibition of the enzyme that was competitive with respect to NADH. Positive chain length effects were observed in the second-order rate constants for inactivation and in the 6-fold better binding of N-heptylmaleimide as compared to that for N-ethylmaleimide. It is suggested that the nonpolar interactions stabilizing the 1,4-dihydronicotinamide moiety of the reduced coenzyme also facilitate the initial binding of N-alkylmaleimides.

Differential response of two cell lines sequentially irradiated with low X-ray doses.

An experiment was designed to compare the effect of repeated low doses of X-rays in two different cell lines: one transformed, epithelial like and aneuploid Chinese hamster ovary K-1 (CHO-K1); the other originated from a human primary culture, fibroblast, diploid and non-transformed, MRC-5. CHO and MRC-5 cells were cultured for 14 or eight passages, respectively. Irradiation was performed once per passage when cells were in the quiescent state (90 - 95% in G1/G0). Cells were exposed to 10.0 mSv X-ray doses. Ionizing radiation did not induce apoptosis or necrosis in the exposed CHO cell population. Significant increases of low-level damaged cells (degrees 1 and 2) were found for the 14 cycles of radiation when compared with controls, except for the first irradiation cycle. No significant increases in the frequency of cells with severe damage were observed. The frequency of MRC-5 cells with low-level damage increased significantly when compared with controls for radiation cycles seven and eight. Significant increases of apoptosis, necrosis and severe damage were found only for the highest dose. Transformed and non-transformed cell types responded differently to direct and indirect damage using low-dose repeat exposures to ionizing radiation. Though more investigation is needed to understand the mechanisms of radiation effects in chronic low-dose-exposed cell populations, cellular type should be taken into account in the design of in vitro experiments for understanding low-dose-irradiation effects.

Role of Helicobacter pylori in stomach cancer after partial gastrectomy for benign ulcer disease.

OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for non-neoplastic disease who later developed gastric stump cancer. MATERIAL AND METHODS: Retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. RESULTS: A total of 73 patients were studied in this period. Fifteen patients (20.5%) had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48) years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p < 0.07). No relationship was seen between type of gastric reconstruction (Billroth I or II) and rate of Helicobacter pylori detection. CONCLUSIONS: Helicobacter pylori infection is frequent in patients with previous gastrectomy for non-neoplastic disease. The results of the study suggest that Helicobacter pylori infection may play a role in gastric stump cancer.

[Helicobacter pylori and gastric cancer: relationship with histological subtype and tumor location]. / Helicobacter pylori y cáncer gástrico: relación entre el subtipo histológico y la localización del tumor.

INTRODUCTION: Helicobacter pylori (HP) has been implicated in the pathogenesis of gastric adenocarcinoma. Published data on HP infection and its association with both histological subtype and tumor localization are contradictory and few data are available on this topic in Spain. The aim of the present study was to evaluate the association of HP infection with histological subtype and tumor localization in a series of patients with gastric adenocarcinoma. MATERIAL AND METHOD: We retrospectively reviewed all the patients diagnosed with gastric neoplasms in Hospital del Mar in Barcelona between 1995 and 2001. The histological subtype was established using Lauren's classification. Tissue samples were obtained from the surgical specimen or from endoscopic biopsies. HP infection was histologically determined through hematoxylin-eosin, Masson's trichromic, and Giemsa staining. RESULTS: During the study period, 304 gastric neoplasms, 275 (90.4%) adenocarcinomas, 22 (7.2%) lymphomas, 3 (1.0%) leiomyosarcomas, 2 (0.7%) degenerated gastrointestinal stromal tumors (GIST) and 2 (0.7%) Kaposi's sarcomas were diagnosed. In patients with adenocarcinoma, the mean age at diagnosis was 69 years and most patients were male (62%). A total of 48.1% of the neoplasms were located in the gastric antrum, 23.7% in the body and 19.1% in the fundus (13.6% in the period 1994-1997 and 25.4% in the period 1998-2001, p = 0.018). Intestinal-type gastric carcinoma was observed in 56% of the patients, diffuse-type in 28% and indeterminate-type in 16%. HP infection was confirmed in 69% of the patients (68% in intestinal subtype, 69% in diffuse subtype, and 69% in indeterminate subtype, p = 0.84), and was significantly associated with distal adenocarcinomas vs. proximal adenocarcinomas (73.6% vs 48.6%, p < 0.05). CONCLUSIONS: No differences were observed between the histological type of adenocarcinoma and HP infection. In the last few years, the incidence of fundic adenocarcinomas has increased. These tumors show a lower association with HP infection.

Relationship between insult intensity and mode of hair cell loss in the vestibular system of rats exposed to 3,3'-iminodipropionitrile.

A variety of stimuli cause sensory hair cell loss in the mammalian inner ear. This loss occurs by several differing processes, the significance of which remains undetermined. This study examines the relationship between the intensity of the damaging stimulus and the mode of hair cell loss found in the vestibular sensory epithelia of the rat. The ototoxin 3,3'-iminodipropionitrile (IDPN) was administered to rats at three different intoxication rates: acute exposure to high doses, repeated exposure to intermediate doses, and subchronic exposure to low doses. The morphology of the vestibular epithelia was examined by light microscopy and by scanning and transmission electron microscopy (SEM and TEM). In addition, DNA fragmentation in the epithelia was assessed by terminal deoxynucleotidyl transferase (tdt)-dUTP-nick-end-label (TUNEL). One day after acute IDPN, necrosis of hair cells was observed. However, at day 4 with this dose, and 1 and 4 days after repeated exposure, apoptotic figures and positive TUNEL labeling predominated. Subchronic IDPN resulted in a slowly evolving extrusion of basically intact hair cells in the crista and utricle. The data demonstrate that extrusion is a major mechanism of hair cell demise in mammals, that necrosis, apoptosis, and extrusion form a continuum of modes of hair cell loss, and that the intensity of the damaging stimulus determines the prevalence of each mode: Necrosis was most evident when the intensity was at its highest, whereas extrusion predominated when the intensity was at the lowest end of the scale.

Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes.

Trypanosoma cruzi epimastigotes permeabilized with digitonin (65 micrograms (mg protein)-1) to measure mitochondrial respiration were exposed to different substrates. Although none of the NADH-dependent substrates stimulated respiration, succinate supported not only oxygen consumption but also oxidative phosphorylation (respiratory control ratio of 1.9 +/- 0.3) indicating that the mitochondria were coupled. The rate of NADH-dependent oxygen consumption by membrane fractions (9.4 +/- 0.7 nmol min-1 (mg protein)-1) was reduced by 50% upon addition of catalase indicating that the electrons from NADH oxidation reduced oxygen to H2O2. NADH-dependent H2O2 production (16 +/- 1 nmol min-1 (mg protein)-1) was confirmed using cytochrome c peroxidase. This activity was inhibited by fumarate by 70%, suggesting a competition between fumarate and oxygen for the electrons from NADH, probably at the fumarate reductase level. The respiratory chain inhibitor antimycin blocked both respiration by intact cells and succinate-dependent cytochrome c by isolated membranes. No inhibition by antimycin was observed when NADH replaced succinate as an electron donor, indicating that the electrons from NADH oxidation reduced cytochrome c through a different route. Malonate blocked not only succinate-cytochrome c reductase and fumarate reductase, but also intact cell motility. These results suggest that succinate has a central role in the intermediate metabolism of i. cruzi, as it may be used for respiration or excreted to the extracellular space under anaerobic conditions. In addition, 2 potential sources of H2O2 were tentatively identified as: (a) the enzyme fumarate reductase; and (b) a succinate-dependent site, which may be the semiquinone form of Coenzyme Q9, as in mammalian mitochondria.

DNA damage in Chinese hamster cells repeatedly exposed to low doses of X-rays.

In a recent paper we reported the results of an experiment carried out by analysing chromosomal damage in Chinese hamster (CHO) cells exposed to low doses of X-rays. The present investigation was undertaken in order to validate those results using a different approach, the single cell gel electrophoresis assay (comet assay) immediately after irradiation. Cells were cultured during 14 cycles, irradiation treatment was performed once per cycle when the cells were at 90-95% of confluence. Doses of 2.5, 5.0 and 10.0 mSv were used. Sequential irradiation of CHO cells induced a decrease of cells without migration and an increase of cells showing DNA damage with the three doses employed. Significant increases of low-level damaged cells (p < 0.001) were found for the 14 exposures when compared to controls except for the first irradiations with 2.5 and 10 mSv, respectively. No significant increase of the frequency of cells with severe damage was observed in any case. These findings could be explained by assuming a complex interactive process of cell recovery, DNA damage and repair together with the induction of genomic instability, the incidence of bystander effects as well as some kind of radioadaptative response of the cells. If these phenomena are limited to the cell line employed deserves further investigation.

Efferent function of vestibular afferent endings? Similar localization of N-type calcium channels, synaptic vesicle and synaptic membrane-associated proteins.

We investigated the distribution of N-type voltage-dependent calcium channels that mediate Ca(2+) entry initiating transmitter release in the rat vestibular sensory epithelium. We used confocal microscopy to assess the in vitro labeling by fluorescent specific ligand binding, omega-conotoxin-GVIA and also the immunolabeling of presynaptic soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor (SNARE) proteins, syntaxin, 25,000 mol. wt synaptosome-associated protein and synaptotagmin: components of the neurotransmitter exocytosis machinery. We found that there was a close anatomical association between the voltage-gated calcium channels, the synaptic vesicle and synaptic membrane-associated proteins on the afferent nerve calyces and probably afferent boutons, which are postsynaptic compartments. Our data suggest that these peripheral afferent endings possess the presynaptic Ca(2+) channels and the components of the presynaptic SNARE proteins involved in synaptic vesicle docking and calcium-dependent exocytosis. They provide additional evidence for a secretory function and efferent role of these endings in hair cell neurotransmission.

Degeneration and gliosis in rat retina and central nervous system following 3,3'-iminodipropionitrile exposure.

3,3'-Iminodipropionitrile (IDPN) exposure causes a neurofilamentous axonopathy and olfactory, audiovestibular and visual toxicity. Many events relevant to these effects and the neurotoxic properties of nitriles as a class remain to be elucidated. We characterized the gliosis associated with the IDPN-induced retinal degeneration in comparison to other effects on the visual and central nervous systems. Gliosis was quantified using an ELISA for the intermediate filament protein, glial fibrillary acidic protein (GFAP). IDPN (0-400 mg kg-1 day-1x3 days, i.p.) caused corneal opacity and dose- and time-dependent increases in retinal GFAP, up to 26-28 fold of control values at 4 weeks post-exposure; a second peak occurred at 16 weeks. In contrast, GFAP peaked at 1 week in olfactory bulbs (OB), cingulate cortex and hippocampus. Cerebellum and striatum showed no gliosis. Retinal dopamine decreased within 2 weeks. Delayed GFAP increases occurred in superior and inferior colliculi. Retina and superior colliculi also showed increased [3H]PK-11195 binding. Histological analysis demonstrated progressive degeneration and gliosis in retina and colliculi. Taken together, the data indicate that primary and secondary degenerative events occur in the retina, and that this retinal degeneration induces GFAP increases in retina and superior colliculus. In addition, GFAP assays demonstrated that the retinal toxicity of IDPN is enhanced by CCl4 hepatotoxicity and blocked by methimazole inhibition of flavin-mono-oxygenases, similarly to its ototoxicity. GFAP assays also indicated that neither vestibulotoxic doses of crotononitrile nor olfatotoxic doses of dichlobenil damage the retina. The data support the use of GFAP assays for assessing the retinal toxicity of IDPN and other nitriles.

Malsegregation as a possible mechanism of aneuploidy induction by metal salts in MRC-5 human cells.

Many aneugenic compounds are known to affect one or more components of the mitotic apparatus leading to an erroneous migration of chromosomes. Malsegregation occurs when a chromosome (or a chromatid) fails to migrate and remains at the metaphase plate. Nondisjunction implies the lack of dissociation between sister chromatids and the migration of both together to the same pole. The aim of the present study was to provide evidence that the aneugenic effect of some metal salts is the consequence of malsegregation at anaphase and that it is not caused by nondisjunction mechanisms. The frequencies of lagging chromosomes at anaphase-telophase of mitosis, hypoploid metaphases, and kinetochore-positive micronuclei induced by cadmium chloride, potassium dichromate, and cacodilic acid (dimethylarsinic acid) in MRC-5 human cells were compared. The data indicate that all the tested compounds are able to induce aneuploidy in MRC-5 human cells. Positive, statistically significant correlations were found when kinetochore-positive micronuclei, hypoploidy, and lagging chromosome frequencies were compared. The results suggest that malsegregation is the main mechanism involved in the induction of aneuploidy by metal salts in MRC-5 cells.

Cytogenetic analysis in Chinese hamster cells chronically exposed to low doses of X-rays.

PURPOSE: It is important to develop simple experimental models to assess the induction of DNA damage and study the different factors involved under controlled conditions. This paper describes the cytogenetic analysis carried out in Chinese hamster cells (CHO) sequentially exposed to very low doses of X-rays. MATERIALS AND METHODS: CHO cells were cultured for 14 passages. Irradiation treatment was performed once per passage, and three irradiation doses were employed: 2.5, 5.0 and 10.0 mSv. RESULTS: Sequential irradiation of CHO cells did not increase the yield of chomatid- or chromosome-type aberrations. However, a significant increase of achromatic lesions (gaps) was found after the first or second X-ray dose, with all three irradiation doses employed. CONCLUSIONS: The variation in the frequency of gaps as well as that in the mitotic index during the 14 cycles of radiation could be an indication of the induction of genomic instability. According to this, continuous rises and falls in the frequency of gaps as well as in the mitotic index reflects the simultaneous induction of endogenous DNA damage, cell death and cell survival.

Genotoxic ability of cadmium, chromium and nickel salts studied by kinetochore staining in the cytokinesis-blocked micronucleus assay.

The aneugenic and clastogenic ability of cadmium chloride(II), cadmium sulfate(II), nickel chloride(II), nickel sulfate(II), chromium chloride(III) and potassium dichromate(IV) have been evaluated through kinetochore-stained micronucleus test. Traditional genotoxicity assays evaluate DNA damage, gene mutations and chromosome breakage. However, these tests are not adequate to detect aneugenic agents that do not act directly on DNA. Staining kinetochores in the cytokinesis-blocked micronucleus assay is a useful way to discriminate between clastogens and aneuploidogens and may allow a rapid identification of aneuploidy-inducing environmental compounds. Human diploid fibroblasts (MRC-5) were employed. All compounds increased micronuclei frequency in a statistically significant way. However, increases in kinetochore-positive micronuclei frequencies were higher than in kinetochore-negative ones. The present work demonstrates the genotoxic ability of the cadmium and chromium salts studied. Aneugenic as well as clastogenic ability could be observed with this assay. Nickel salts, as it was expected because of their known weak mutagenicity, showed lower genotoxic effects than the other metal salts studied. As the test employed only allows the detection of malsegregation, it is proposed that this mechanism is at least one of those by which the tested metal salts induced aneuploidy. On the other hand, visualization of kinetochores in all experiments suggests that the compounds studied did not act by damaging these structures.