Toxoplasma gondii IgG Serointensity Is Positively Associated With Frailty.

BACKGROUND: Persistent inflammation related to aging ("inflammaging") is exacerbated by chronic infections and contributes to frailty in older adults. We hypothesized associations between Toxoplasma gondii (T. gondii), a common parasite causing an oligosymptomatic unremitting infection, and frailty, and secondarily between T. gondii and previously reported markers of immune activation in frailty. METHODS: We analyzed available demographic, social, and clinical data in Spanish and Portuguese older adults [N = 601; age: mean (SD) 77.3 (8.0); 61% women]. Plasma T. gondii immunoglobulin G (IgG) serointensity was measured with an enzyme-linked immunosorbent assay. The Fried criteria were used to define frailty status. Validated translations of Mini-Mental State Examination, Geriatric Depression Scale, and the Charlson Comorbidity Index were used to evaluate confounders. Previously analyzed biomarkers that were significantly associated with frailty in both prior reports and the current study, and also related to T. gondii serointensity, were further accounted for in multivariable logistic models with frailty as outcome. RESULTS: In T. gondii-seropositives, there was a significant positive association between T. gondii IgG serointensity and frailty, accounting for age (p = .0002), and resisting adjustment for multiple successive confounders. Among biomarkers linked with frailty, kynurenine/tryptophan and soluble tumor necrosis factor receptor II were positively associated with T. gondii serointensity in seropositives (p < .05). Associations with other biomarkers were not significant. CONCLUSIONS: This first reported association between T. gondii and frailty is limited by a cross-sectional design and warrants replication. While certain biomarkers of inflammaging were associated with both T. gondii IgG serointensity and frailty, they did not fully mediate the T. gondii-frailty association.

Multiclass Segmentation of Breast Tissue and Suspicious Findings: A Simulation-Based Study for the Development of Self-Steering Tomosynthesis.

In breast tomosynthesis, multiple low-dose projections are acquired in a single scanning direction over a limited angular range to produce cross-sectional planes through the breast for three-dimensional imaging interpretation. We built a next-generation tomosynthesis system capable of multidirectional source motion with the intent to customize scanning motions around "suspicious findings". Customized acquisitions can improve the image quality in areas that require increased scrutiny, such as breast cancers, architectural distortions, and dense clusters. In this paper, virtual clinical trial techniques were used to analyze whether a finding or area at high risk of masking cancers can be detected in a single low-dose projection and thus be used for motion planning. This represents a step towards customizing the subsequent low-dose projection acquisitions autonomously, guided by the first low-dose projection; we call this technique "self-steering tomosynthesis." A U-Net was used to classify the low-dose projections into "risk classes" in simulated breasts with soft-tissue lesions; class probabilities were modified using post hoc Dirichlet calibration (DC). DC improved the multiclass segmentation (Dice = 0.43 vs. 0.28 before DC) and significantly reduced false positives (FPs) from the class of the highest risk of masking (sensitivity = 81.3% at 2 FPs per image vs. 76.0%). This simulation-based study demonstrated the feasibility of identifying suspicious areas using a single low-dose projection for self-steering tomosynthesis.

Spatial dependency of lesion detectability in digital breast tomosynthesis.

X-ray imaging results in inhomogeneous irradiation of the detector and distortion of structures in the periphery of the image; yet the spatial dependency of tomosynthesis image-quality metrics has not been extensively investigated. In this study, we use virtual clinical trials to quantify the spatial dependency of lesion detectability in our lab's next-generation tomosynthesis (NGT) system. Two geometries were analyzed: a conventional geometry with mediolateral source motion, and a NGT geometry with T-shaped motion. Breast parenchymal texture was simulated using an open-source library with Perlin noise using 400 random seeds and three breast densities. Spherical mass lesions were inserted in the central slice of the phantoms using the voxel additive method. Image acquisition was simulated using in-house ray-tracing software and simple backprojection was performed using commercial reconstruction software. Lesion detectability with Channelized Hotelling Observers (CHOs) was analyzed using receiver operating characteristic curves to measure the detectability index (d') at 154 unique locations for the lesions. We also divided images into three non-overlapping regions (differing in terms of distance from the chest wall). At the 0.05 level of significance, there was a statistically significant difference between the geometries in terms of d' in one of the three regions, with the T geometry offering superior detectability. Examining all 154 lesion locations, the T geometry was found to offer lower spread (standard deviation) in d' values throughout the image area, and superior d' at 83 of 154 locations (53.9%). In summary, the T geometry enables superior lesion detection and mitigates anisotropies.

Novel Perlin-based Phantoms Using 3D Models of Compressed Breast Shape and Fractal Noise.

Virtual clinical trials (VCTs) have been used widely to evaluate digital breast tomosynthesis (DBT) systems. VCTs require realistic simulations of the breast anatomy (phantoms) to characterize lesions and to estimate risk of masking cancers. This study introduces the use of Perlin-based phantoms to optimize the acquisition geometry of a novel DBT prototype. These phantoms were developed using a GPU implementation of a novel library called Perlin-CuPy. The breast anatomy is simulated using 3D models under mammography cranio-caudal compression. In total, 240 phantoms were created using compressed breast thickness, chest-wall to nipple distance, and skin thickness that varied in a {[35, 75], [59, 130), [1.0, 2.0]} mm interval, respectively. DBT projections and reconstructions of the phantoms were simulated using two acquisition geometries of our DBT prototype. The performance of both acquisition geometries was compared using breast volume segmentations of the Perlin phantoms. Results show that breast volume estimates are improved with the introduction of posterior-anterior motion of the x-ray source in DBT acquisitions. The breast volume is overestimated in DBT, varying substantially with the acquisition geometry; segmentation errors are more evident for thicker and larger breasts. These results provide additional evidence and suggest that custom acquisition geometries can improve the performance and accuracy in DBT. Perlin phantoms help to identify limitations in acquisition geometries and to optimize the performance of the DBT prototypes.

Multiclass Segmentation of Suspicious Findings in Simulated Breast Tomosynthesis Images Using a U-Net.

Our lab has built a next-generation tomosynthesis (NGT) system utilizing scanning motions with more degrees of freedom than clinical digital breast tomosynthesis systems. We are working toward designing scanning motions that are customized around the locations of suspicious findings. The first step in this direction is to demonstrate that these findings can be detected with a single projection image, which can guide the remainder of the scan. This paper develops an automated method to identify findings that are prone to be masked. Perlin-noise phantoms and synthetic lesions were used to simulate masked cancers. NGT projections of phantoms were simulated using ray-tracing software. The risk of masking cancers was mapped using the ground-truth labels of phantoms. The phantom labels were used to denote regions of low and high risk of masking suspicious findings. A U-Net model was trained for multiclass segmentation of phantom images. Model performance was quantified with a receiver operating characteristic (ROC) curve using area under the curve (AUC). The ROC operating point was defined to be the point closest to the upper left corner of ROC space. The output predictions showed an accurate segmentation of tissue predominantly adipose (mean AUC of 0.93). The predictions also indicate regions of suspicious findings; for the highest risk class, mean AUC was 0.89, with a true positive rate of 0.80 and a true negative rate of 0.83 at the operating point. In summary, this paper demonstrates with virtual phantoms that a single projection can indeed be used to identify suspicious findings.

Kinetics of radium-223 and its effects on survival, proliferation and DNA damage in lymph-node and bone metastatic prostate cancer cell lines.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is associated with a very unfavorable prognosis. At this advanced stage of the disease, there are several therapeutic strategies approved in recent times, being one of them Radium-223 dichloride (Radium-223). However, its mechanisms of action and the process that conducts to cell death are not fully understood. Given this, our main goal is to characterize the radiobiological effects induced by Radium-223 and to evaluate its kinetics on metastatic Prostate Cancer (mPCa) cells. MATERIALS AND METHODS: In vitro studies were conducted using two mPCa cell lines, the LNCaP and PC3, the first being derived from lymph node metastasis and the second from bone metastasis. Kinetic studies were conducted to access the capacity of these cell lines to uptake, retain and internalize the Radium-223. For the assessment of radiobiological effects, cells were first exposed to different doses of Radium-223 and the clonogenic assay was done to evaluate cell survival and to determine lethal doses (LD50). Then, the effects were also evaluated in terms of proliferation, oxidative stress, morphological changes and cell damage. RESULTS: Radium-223 is uptaken by mPCa cells and reaches the nucleus, where it is retained over time. Irradiation decreases cell survival and proliferation, with LNCaP cells (LD50 = 1.73mGy) being more radiosensitive than PC3 cells (LD50 = 4.20mGy). Irradiated cells showed morphological changes usually associated with apoptosis and a dose-dependent increase in DNA damage. Moreover, activation of cell cycle checkpoints occurs through ATM/CHK2 pathway, which is involved in cell cycle arrest and cell death. CONCLUSIONS: The cytotoxic and anti-proliferative effects on both cell lines showed that Radium-223 can decrease the aggressiveness of tumor cells by decreasing the cell survival and proliferation and, also, by increasing the DNA damage. The similar results observed in both cell lines indicated that Radium-223 may have the potential to be used as a therapeutic option also for mCRPC patients with lymph node metastasis. The activation of DNA Damage Response pathways allows the possibility to understand the importance of these checkpoints as targets for new combined therapies.

Oxidative Stress and DNA Damage: Implications in Inflammatory Bowel Disease.

This review will focus on published human studies on oxidative stress and DNA damage in inflammatory bowel disease (IBD), both ulcerative colitis and Crohn's disease, assessing their role in the pathophysiology of these diseases. Search was performed over PubMed and ScienceDirect databases to identify relevant bibliography, using keywords including "oxidative stress," "DNA damage," "IBD," and "oxidative DNA damage." Whether as cause or effect, mechanisms underlying oxidative stress have the potential to condition the course of various pathologies, particularly those driven by inflammatory scenarios. IBDs are chronic inflammatory relapsing conditions. Oxidative stress has been associated with some of the characteristic clinical features exhibited in IBD, namely tissue injury and fibrosis, and also to the ulcerative colitis-associated colorectal cancer. The possible influence of oxidative stress over therapeutic behavior and response, as well as their contribution to the oxidative burden and consequences, is also addressed. Due to the high prevalence and incidence of IBD worldwide, and also to its associated morbidity, complications, and disease and treatment costs, it is of paramount importance to better understand the pathophysiology of these diseases.

Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde.

Formaldehyde (FA) is a commonly used chemical in anatomy and pathology laboratories as a tissue preservative and fixative. Because of its sensitising properties, irritating effects and cancer implication, FA accounts probably for the most important chemical-exposure hazard concerning this professional group. Evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting, particularly in regard to the ability of inhaled FA to induce toxicity on other cells besides first contact tissues, such as buccal and nasal cells. To evaluate the effects of exposure to FA in human peripheral blood lymphocytes, a group of 84 anatomy pathology laboratory workers exposed occupationally to FA and 87 control subjects were tested for chromosomal aberrations (CAs) and DNA damage (comet assay). The level of exposure to FA in the workplace air was evaluated. The association between genotoxicity biomarkers and polymorphic genes of xenobiotic-metabolising and DNA repair enzymes were also assessed. The estimated mean level of FA exposure was 0.38±0.03 ppm. All cytogenetic endpoints assessed by CAs test and comet assay % tail DNA (%TDNA) were significantly higher in FA-exposed workers compared with controls. Regarding the effect of susceptibility biomarkers, results suggest that polymorphisms in CYP2E1 and GSTP1 metabolic genes, as well as, XRCC1 and PARP1 polymorphic genes involved in DNA repair pathways are associated with higher genetic damage in FA-exposed subjects. Data obtained in this study show a potential health risk situation of anatomy pathology laboratory workers exposed to FA (0.38 ppm). Implementation of security and hygiene measures may be crucial to decrease risk. The obtained information may also provide new important data to be used by health care programs and by governmental agencies responsible for occupational health and safety.

Neuroprotective effect of steroidal alkaloids on glutamate-induced toxicity by preserving mitochondrial membrane potential and reducing oxidative stress.

Several evidences suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of several neurodegenerative diseases. The aim of this study was to investigate for the first time whether both extracts from tomato plant (Lycopersicon esculentum Mill.) leaves and their isolated steroidal alkaloids (tomatine and tomatidine) afford neuroprotective effect against glutamate-induced toxicity in SH-SY5Y neuroblastoma cells and to elucidate the mechanisms underlying this protection. Steroidal alkaloids from tomato are well known for their cholinesterases' inhibitory capacity and the results showed that both purified extracts and isolated compounds, at non-toxic concentrations for gastric (AGS), intestinal (Caco-2) and neuronal (SH-SY5Y) cells, have the capacity to preserve mitochondria membrane potential and to decrease reactive oxygen species levels of SH-SY5Y glutamate-insulted cells. Moreover, the use of specific antagonists of cholinergic receptors allowed observing that tomatine and tomatidine can interact with nicotinic receptors, specifically with the α7 type. No effect on muscarinic receptors was noticed. In addition to the selective cholinesterases' inhibition revealed by the compounds/extracts, these results provide novel and important insights into their neuroprotective mechanism. This work also demystifies the applicability of these compounds in therapeutics, by demonstrating that their toxicity was overestimated for long time.

Comet assay reveals no genotoxicity risk of cationic solid lipid nanoparticles.

Cationic solid lipid nanoparticles (cSLN) are colloidal carriers for genes or drugs, particularly lipophilic drugs. Several reports exist on their high efficiency, but only a few studies report the effect of cSLNs on living cells. In the present work, internalization, cell viability (alamar blue assay) and genotoxic potential (alkaline comet assay) of three cSLN formulations (A-C) were evaluated in HepG2 and Caco-2 cells. cSLN showed an average hydrodynamic diameter (z-ave) of 141-222 nm, zeta-potential of 55.0-72.5 mV and polidispersity indices (PdI) of 0.336-0.421. Dispersion in physiological buffers increased z-ave and PdI. 0.01 mg ml(-1) cSLN unaffected cell viability, but 1.0 mg ml(-1) significantly decreased it, being cSLN-C (Compritol-based) the most toxic and HepG2 the most affected. DNA damage was not significantly increased by 0.1 mg ml(-1) cSLN but damage was observed at 1.0 mg ml(-1) cSLN-C. Thus, no genotoxicity is to be expected at concentrations that do not reduce cell viability.

Effects of titanium dioxide nanoparticles in human gastric epithelial cells in vitro.

Manufacturing or using nanomaterials may result in exposure of workers to nanoparticles. Potential routes of exposure include skin, lung and gastrointestinal tract. The lack of health-based standards for nanomaterials combined with their increasing use in many different workplaces and products emphasize the need for a reliable temporary risk assessment tool. Therefore, the aim of this work was to explore the effects of different doses of titanium dioxide nanoparticles on human gastric epithelial cells in vitro. We analyzed proliferation by MTT assay, apoptosis by Tunel, migration by injury assay, oxidative stress by determining GSH/GSSG ratio and DNA damage by Comet assay on nanoparticle-treated AGS human gastric epithelial cell line in comparison to controls. We show and discuss the tumor-like phenotypes of nanoparticles-exposed AGS cells in vitro, as increased proliferation and decreased apoptosis. Our results demonstrate for the first time that nanoparticles induce tumor-like phenotypes in human gastric epithelial cells.

Multiple genotoxic activities of ptaquiloside in human lymphocytes: aneugenesis, clastogenesis and induction of sister chromatid exchange.

Ptaquiloside, a norsesquiterpene glycoside from bracken (Pteridium aquilinum), is a known carcinogen towards animals. Its genotoxicity is mainly attributed to its DNA-alkylating and clastogenic properties. This study analyses various modes of genotoxic action of ptaquiloside in human mononuclear blood cells. The alkaline comet assay was performed on cells exposed to 5µg/ml ptaquiloside for 5, 10, 20, 30, 40 or 50min. Tail length was used as a DNA-damage parameter. Assays to determine structural and numerical chromosomal aberrations and sister-chromatid exchange were conducted on cells exposed to 5, 10 or 20µg/ml ptaquiloside for 48h. The tail length showed maximum DNA damage at 20-30min, diminishing onwards. Highly significant (p<0.001) dose-dependent increases in structural and numerical chromosomal aberrations and SCE were observed in response to ptaquiloside. These results indicate that ptaquiloside is not only a DNA-alkylating agent, but expresses its genotoxicity through multiple mechanisms including clastogenesis, aneugenesis and the mechanism underlying SCE induction, which is not entirely understood. Recent studies support the role played by aneuploidy in oncogenesis, highlighting the importance of this endpoint for mutagenicity screening. SCE are thought to represent the long-term effects of mutagens and are an important genotoxicity biomarker. The present results also agree with data from epidemiological studies and from animal in vivo studies, further supporting the hypothesis that ptaquiloside may represent a significant threat to human health.

Chemical exposure and occupational symptoms among Portuguese hairdressers.

Hairdressing is predominantly a female activity, in which several chemicals are handled, some of which are known to be allergenic and potentially carcinogenic. Several epidemiological studies showed an association between occupational exposure to chemicals in hairdressing salons and skin and respiratory-tract conditions. The aim of this study were to characterize the occupational exposure to total volatile organic compounds (VOC) and ammonia (NH3) in 50 Portuguese hairdressers' salons and to analyze the prevalence of respiratory and skin symptoms in 134 hairdressing professionals. Data indicated that internal sources of total VOC are mainly due to indoor sources, with average concentrations (1.4 mg/m³) above the Portuguese reference levels (0.6 mg/m³). Of the hairdressers' salons studied, 4% had a mean NH3 concentration higher than Portuguese (20 ppm) and American Conference of Industrial Hygienists (ACGIH) (25 ppm) reference levels. Hand dermatitis was the occupational symptom most reported by hairdressers (50%), followed by eye irritation (43%). The results of this study suggest that hairdressers' occupational activities are linked with higher risk of developing hand and wrist/arm dermatitis and symptoms in the upper respiratory tract. The proper use of disposable gloves, hands, wrists, and arms skin monitoring, and the frequent use of moisturizers in the workplace are effective measures to prevent the occurrence of dermatitis in these professionals. Displacement ventilation and/or local exhaust with adequate air exchange rate are recommended particularly in technical areas where hairdressing chemicals are mixed.

Genetic effects and biotoxicity monitoring of occupational styrene exposure.

Styrene is a commercially important chemical widely used in the manufacture of synthetic rubber, resins, polyesters, and plastics. The highest levels of human exposure to styrene occurs in occupational settings, especially during the production of reinforced plastic products, which involve manual lay-up or spray-up operations. In these settings, absorption of styrene occurs mainly through inhalation and, to a minor extent, via skin contact. A variety of biological markers (biomarkers) have been developed for genotoxic agents. Three types of biomarkers are identified: biomarkers of exposure, of effect and of susceptibility. Biomarkers of exposure measure the chemical itself or its metabolites in body fluids. Biomarkers of effect measure indicators of damage by the exposure. Biomarkers of effect are generally pre-clinical indicators of abnormalities and the most frequently used in genotoxicity assessment are sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronuclei (MN). More recently, the use of the single cell gel electrophoresis assay (SCGE), or comet assay has been proposed as a useful biomarker for early effects. The third type is a biomarker of susceptibility, which indicates that the individual is vulnerable to the effect of a xenobiotic or to the effects of a group of such compounds. This type of biomarkers are related with individual genetic polymorphisms that could lead to different capacities to activate, detoxify or repair DNA lesions arising from exposure to chemical carcinogens. Styrene metabolism involves cytochrome P450 enzymes (CYP)-mediated that by oxidation convert styrene to its reactive metabolite styrene-7,8-oxide (SO) which is capable of binding covalently with macromolecules and is considered to be directly responsible for the genotoxic effects of styrene. SO, is mainly hydrolysed to styrene glycol by the microsomal epoxide hydrolase (mEH), and subsequently oxidized by alcohol and aldehyde dehydrogenases to the main urinary metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA) (major pathway). MA and PGA represent more than 95% of the urinary metabolites of styrene. Further transformation of MA and PGA, via transamination of alpha-keto- and alpha-hydroxyacids into the corresponding amino acid, leads to phenylglycine. Evidence of the carcinogenicity of styrene has been reported in studies with mice. Epidemiologic evidence does not suggest a causal association between styrene and any forms of cancer in humans. However, the possibility of a small elevation of risk for one or more cancers cannot be ruled out. The International Agency for Research on Cancer (IARC) has designated styrene as possibly carcinogenic to humans (group 2B). Concern about the potential carcinogenicity of styrene stems largely from the ability of its metabolite, SO to bind covalently to DNA and to its activity in a variety of genotoxicity test systems. SO has been classified by IARC in group 2A, probably carcinogenic to humans. Styrene exposure has been reported to cause an increase in DNA and haemoglobin adducts and in the frequency of CAs; there is less evidence for an association between styrene exposure and the frequency of SCEs. This article thoroughly reviews all available published data on the genetic effects of styrene and the biotoxicity markers of exposure monitoring.

Cytogenetic and molecular biomonitoring of a Portuguese population exposed to pesticides.

Widespread use of pesticides in agriculture represents a threat not only to the environment but also to human populations exposed to them. Many of these compounds are capable of inducing mutations in DNA and lead to several diseases including cancer. In the present study, cytogenetic damage in peripheral lymphocytes from 33 farmers of Oporto district (Portugal) exposed to pesticides was evaluated by means of micronuclei (MN), sister chromatid exchange (SCE) and chromosomal aberrations (CA). In addition, effect of polymorphic genes of xenobiotic metabolizing enzymes (GSTM1, GSTT1, GSTP1, CYP2E1 and EPHX1) was also evaluated. A non-exposed group from the same area and with same demographic characteristics without exposure to genotoxic compounds was studied and data obtained from both groups was compared. MN and SCE frequencies were significantly higher in the exposed group (P < 0.005). In what concerns CA results, no significant differences were observed. It was possible to relate a specific working environment (greenhouses) with higher levels of genetic damage. Use of personal protective equipment revealed to be important to prevent exposure and diminish genetic damage inflicted by pesticides. Allele frequencies of studied polymorphic genes obtained in this study are similar to the ones described by other authors for Caucasian populations. Despite the low number of subjects, results suggest that low mEH (microsomal epoxide hydrolase) activity as well as GSTT1 positive genotype are associated with increased cytogenetic damage.

Evaluation of genotoxicity in a group of workers from a petroleum refinery aromatics plant.

Petroleum refinery workers are potentially exposed to a wide range of petroleum-derived hydrocarbons and chemical substances used in the manufacturing of petroleum derivatives. Benzene, toluene and xylene (BTX) are produced by distillation in the aromatics units and used as raw materials for petrol and petrochemical products. The aim of this study was to evaluate the genotoxic effects of occupational exposure to BTX in a petroleum refinery in the North of Portugal. The exposed group consisted of 48 workers from the aromatics plant and the control group consisted of 30 persons matched for various confounding factors. Chromosome aberrations (CA), micronuclei (MN), and DNA damage (evaluated by means of the comet assay) were measured in peripheral blood leukocytes. t,t-Muconic acid (t,t-MA), hippuric acid (HA) and methylhippuric acid (MHA) concentrations were measured in urine samples collected at the end of the workshift. The results suggest that occupational exposure to toluene and xylene is very low. A statistically significant increase in t,t-MA excretion was found in the exposed group although t,t-MA levels were found to be lower than the biological exposure index (BEI). Significant increases were found for CA, MN and comet tail length (TL) in the exposed group (p<0.05). No association was found between tobacco smoking and the effect biomarkers analysed. A positive association was found between CA and MN with age in the control group (p<0.05).

Occupational exposure to styrene: modulation of cytogenetic damage and levels of urinary metabolites of styrene by polymorphisms in genes CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1.

Styrene is widely used in the production of various plastics, synthetic rubber and resins. The aim of this study was to evaluate if individual polymorphisms in xenobiotic metabolizing enzymes, related with the metabolic fate of styrene, could modify individual susceptibility to the possible genotoxic effects of the styrene exposure. Twenty-eight reinforced plastic workers and 28 control subjects were studied. In the selected population the urinary styrene metabolites mandelic (MA) and phenylglyoxylic (PGA) acids were quantified, sister chromatid exchanges (SCE) and micronuclei (MN) were assessed in peripheral lymphocytes and all the subjects were genotyped for GSTM1, GSTT1 (gene deletions), GSTP1 (codon 105 ile==>val), EPHX1 (codons 113 tyr==>his and 139 his==>arg) and CYP2E1 (DraI polymorphism in intron 6). The results obtained showed a significant difference between the levels of SCE, but not in MN levels, in exposed workers as compared with the control group. The GSTP1 and CYP2E1 individual genotypes modulate the baseline levels of SCE that are lower in non-wild type individuals for both polymorphisms. The GSTM1 null individuals with low levels of exposure have significantly higher urinary levels of MA+PGA. The present data seem to suggest that apart from the methodology usually used for monitoring populations occupationally exposed to styrene (urinary metabolites and biomarkers of early biological effects) the analysis of individual genotypes associated with the metabolic fate of styrene should also be carried out in order to evaluate the individual genetic susceptibility of exposed populations.