Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Absorption of arsenic from soil and water by two chard (Beta vulgaris L.) varieties: A potential risk to human health.

The accumulation of arsenic (As) in vegetables poses a risk of contamination to humans via the food chain. Two chard (var. cicla and var. d'ampuis) crops were grown for 60 days in greenhouses on Aridisol soil, and irrigated with water from Pastos Chicos, Jujuy (Argentina). The soil and water used in the trial presented 49 and 1.44 mg/L As concentration levels, respectively. Total dry biomass (TDB) and total As were determined in soils, roots and leaves. The latter was quantified by atomic absorption spectrometry with hydride generation, and bioconcentration and translocation factors were determined. TDB in var. cicla showed statistically significant differences when the plant was cultivated in control soil and watered with the toxicant (2.04 g), as compared with the treatment without exposure (2.8 g). TDB in var. d'ampuis presented statistically significant differences with respect to that of the control when the plants were grown in soils with As and watered with the toxicant (3.3 g). This variety increased its biomass in the presence of As. In the two Swiss chard varieties evaluated, the largest As accumulation in root and leaves was found when they were cultivated in contaminated soil and watered with distilled water. The presence of the toxicant in the leaves exceeded the limits established by Código Alimentario Argentino, i.e. 0.30 mg/kg. Total target hazard quotient (THQ) values for As were higher than 1, suggesting that consumers would run significant risks when consuming these chard varieties. Furthermore, it was determined that the carcinogenic risk (CR) posed by this type of exposure to As exceeded the acceptable risk level of 1 × 10-6. Based on this evidence, we may conclude that consuming chard cultivated on the evaluated site brings about considerable risks to local residents' health.

Experience with anidulafungin in patients with allogeneic hematopoietic stem cell transplantation and graft-versus-host disease.

BACKGROUND: It is well known that both acute and chronic graft-versus-host disease (GVHD) are associated with invasive fungal disease (IFD). Because the galactomannan antigen diagnostic test has low specificity and sensitivity outside of the neutropenic period, many institutions use posaconazole or voriconazole for IFD prophylaxis during GVHD treatment. Moreover, several factors, mainly hepatic impairment, can limit the use of extended spectrum azoles, both in prophylaxis or treatment. METHODS: We retrospectively analyzed 25 patients with allogeneic hematopoietic stem cell transplantation (HSCT) and GVHD - grade III-IV acute GHVD (n = 15), progressive chronic GVHD (n = 7), and "overlap" GVHD (n = 3) - who received intravenous anidulafungin (200 mg on day 1, followed by 100 mg once daily). If necessary, anidulafungin treatment was followed by oral administration of 200 mg voriconazole twice a day or 200 mg posaconazole 3 times daily until patients were considered not at risk for IFD. RESULTS: Twenty-one patients (85%) received anidulafungin as prophylaxis and 5 patients (15%) received it as treatment. Median duration of intravenous anidulafungin administration was 8 days (range 6-17). Seven patients (28%) presented mild adverse effects, with no significant interactions with calcineurin inhibitors. Sequentially, 4 patients received voriconazole and 6 posaconazole. Two patients (8%) developed IFD after anidulafungin withdrawal: 1 with Candida albicans and the other with Mucor, 8 and 5 days after withdrawal, respectively. CONCLUSIONS: Our results are of interest owing to the absence of data in the literature on anidulafungin use in HSCT patients with GVHD, and suggest that anidulafungin, because of its spectrum, pharmacological profile, low toxicity, and absence of interactions with immunosuppressants, could be a drug of choice in this setting.

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

Assessment of exposure to lead in humans and turtles living in an industrial site in Coatzacoalcos Veracruz, Mexico.

The intake of lead from the environment may occur thru various receptors. In order to measure lead levels absorbed, samples were taken from Children who live in three localities surrounding an industrial complex in Coatzacoalcos, Veracruz. Samples were also taken from turtles. Samples were analyzed and results were compared against the general population. In children tested, over 75% of all values were determined to be above CDC's safety levels of (10 µg/dL). The geometric mean lead concentration was 11.4 µg/dL, which is clearly higher around the industrial complex than in the general population. In turtles, lead blood levels in the exposed population were 2-fold above (24.2 µg/dL) those of turtles in the reference population (10.1 µg/dL). Lead levels observed represent a risk for both human and fauna health.

Assessment of dioxin-like soil contamination in Mexico by enzyme-linked immunosorbent assay.

In this work, we describe the results of a preliminary soil assessment program for the detection of dioxins at different sites in Mexico performed by immunoassay. We studied five different sectors considered relevant sources of dioxins: Anaversa and Tekchem industrial areas where organochlorine pesticides were manufactured and released by accidental explosions, secondary smelters, brick kilns, and rural dwellings. In the context of the Agency for Toxic Substances and Disease Registry (ATSDR) guidelines, only the brick kilns sites can be considered as low-risk areas. The dioxin concentrations detected in the vicinity of the Anaversa and Tekchem chemical plants and secondary smelters exceed the screening level of 0.05 ppb set by the ATSDR, and therefore further site-specific studies are needed. The dioxin levels found in all soot samples from indigenous dwellings where wood is used for indoor cooking were above the evaluation level. Considering that the studied areas are representative examples of dioxin sources in less developed countries, our work demonstrates the useful application of dioxin immunoassays as a tool for dioxin screening for environmental assessment programs in developing countries.

In silico analysis of antidiabetic potential of phenolic compounds from blue corn (Zea mays L.) and black bean (Phaseolus vulgaris L.).

The growing interest in bioactive compounds, especially in polyphenols, is due to their abundance in the human diet and potentially positive effects on health. The consumption of polyphenols has been shown to possess anti-diabetic properties by preventing insulin resistance or insulin secretion through different signaling pathways, this effect is associated with their capacity to exert genomic modulations. Several studies have suggested that polyphenols could also bind to cellular proteins and modulate their activity, however, the mechanisms of action underlying their beneficial effects are complex and are not fully understood. The aim of this work was to characterize phenolic compounds present in blue corn and black bean extracts as well as identify their potential interactions with target proteins involved in diabetes pathogenesis using in silico approach. Total polyphenols content of both blue corn and black beans was identified using UPLC-ESI/qTOF/MS and quantified by colorimetric assays. In this work we identified twenty-eight phenolic compounds in the extracts, mainly anthocyanins, flavonols, hydroxycinamic acids, dihydroxybenzoic acids, flavones, isoflavones, and flavanols. Interactome of these compounds with thirteen target proteins involved in type 2 diabetes mellitus was performed in-silico. In total, 312 bioactive compounds/protein interaction analyses were acquired. Molecular docking results highlighted that nine of the top ten interactions correspond to anthocyanins, cyanidin 3-glucoside with 11ß-HS, GFAT, PPARG; delphinidin 3-glucoside with 11ß-HS, GFAT, PTP and RTKs; and petunidin 3-glucoside with 11ß-HS and PTP. These proteins are involved in mechanisms regulating functions such as inflammation, insulin resistance, oxidative stress, glucose and lipid metabolism. In conclusion, this work provides a prediction of the potential molecular mechanism of black bean and blue corn polyphenols, specifically anthocyanins and could constitute new pathways by which compounds exert their antidiabetic benefits.

Arsenic accumulation in lettuce (Lactuca sativa L.) and broad bean (Vicia faba L.) crops and its potential risk for human consumption.

Exposure to arsenic (As) is considered one of the primary health risks humans face worldwide. This study was conducted to determine As absorption by broad beans and lettuce crops grown in soil with As contents and irrigated with water contaminated with this toxic element, in Pastos Chicos, Jujuy (Argentina). Total dry biomass (TDB) and total As were determined in soils, roots, leaves, pods and seeds. These data were used to determine several parameters, such as translocation (TF) and bioconcentration (BCF) factors, target hazard quotient (THQ), and carcinogenic risk (CR). Broad bean plants had the lowest biomass production when exposed to As in irrigation water and soil. Lettuce plants presented TDB reductions of 33.3 and 42.8% when grown in soil polluted with As, and in control soil under irrigation with contaminated water, respectively. The presence of this toxicant in broad bean seeds and lettuce leaves (edible parts) exceeded the limits established by Código Alimentario Argentino, i.e. 0.10 and 0.30 mg/kg, respectively. THQ values for lettuce leaves were higher than 1, the same as those for broad bean seeds when grown in soil with As contents and irrigated with arsenic-contaminated water, thus suggesting that consumers would run significant risks when consuming these vegetables. Furthermore, this type of exposure to As implied a CR that exceeded the acceptable 1 × 10-4 risk level. Hence, we may conclude that consuming lettuce and broad beans grown at the evaluated site brings about considerable health risks for local residents.

Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation.

Chronic lymphocytic leukemia (CLL), the most frequent form of adult leukemia in Western countries, is characterized by a highly variable clinical course. Expression profiling of a series of 160 CLL patients allowed interrogating the genes presumably playing a role in pathogenesis, relating the expression of functionally relevant signatures with the time to treatment. First, we identified genes relevant to the biology and prognosis of CLL to build a CLL disease-specific oligonucleotide microarray. Second, we hybridized a training series on the CLL-specific chip, generating a biology-based predictive model. Finally, this model was validated in a new CLL series. Clinical variability in CLL is related with the expression of two gene clusters, associated with B-cell receptor (BCR) signaling and mitogen-activated protein kinase (MAPK) activation, including nuclear factor-kappaB1 (NF-kappaB1). The expression of these clusters identifies three risk-score groups with treatment-free survival probabilities at 5 years of 83, 50 and 17%. This molecular predictor can be applied to early clinical stages of CLL. This signature is related to immunoglobulin variable region somatic hypermutation and surrogate markers. There is a molecular heterogeneity in CLL, dependent on the expression of genes defining BCR and MAPK/NF-kappaB clusters, which can be used to predict time to treatment in early clinical stages.

Biomonitoring of persistent organic pollutants (POPs) in child populations living near contaminated sites in Mexico.

The aim of this study was to conduct a POP biomonitoring programme for children in high-risk areas. We evaluated 247 serum samples from children between the ages of 6 and 12years old from two zones in Mexico: (1) indigenous zones, which included Cuatlamayan (CUA), Tocoy (TOC), and Santa Maria Picula (SAM); and (2) industrial zones, which included Tercera Chica (TC), Industrial San Luis (IND) and Rincon de San Jose (SJR); Mundo Nuevo (MN); and Alpuyeca (ALP). Our results showed that α-endosulfan was similar to CUA, TOC, SAM, TC and MN (178.6-306.9ng/g lipid). ß-Endosulfan levels were higher in ALP (901.5ng/g lipid), followed by CUA (139.9ng/g lipid) and TOC, SAM, TC and MN, which had similar levels (55.4-64.5ng/g lipid). For endosulfan sulfate, the ALP community had the highest concentration levels (1096.4ng/g lipid), whereas CUA and TOC (212.3 and 289ng/g lipid, respectively) had concentrations similar to those found in SAM and TC (99.5 and 119.1ng/g lipid, respectively). DDE levels were found in malaria-endemic areas of SAM, CUA and TOC (1782.2, 1358.3 and 57.0ng/g lipid), followed by MN (35.1ng/g lipid). HCB concentration levels were found to be higher in MN and SJR (691.8 and 575.4ng/g lipid, respectively), followed by CUA and TC (363.9 and 269.1ng/g lipid, respectively), with levels similar to those found in TOC and SAM (191.8 and 181.9ng/g lipid, respectively). Finally, PCB 101 concentration levels were found to be the highest in ALP (1032.7ng/g lipid), followed by similar levels of SJR and IND (567.5 and 327.3ng/g lipid, respectively) and TC and MN, with 109.1 and 144.5ng/g lipid, respectively. The evidence provided by this exploratory study indicates that the evaluation of the health risks posed to children living in contaminated areas is a high priority health issue.

c-K-ras mutations in human carcinomas occur preferentially in codon 12.

A study was carried out to determine the frequency and distribution of mutations in the c-K-ras gene in human carcinoma tissue. The study was done on a total of 51 lung, colon and breast carcinoma tumors using a panel of oligonucleotides coding for the wild type and all possible mutations in codons 12 and 61 of c-K-ras gene. Four of 16 colon carcinomas, two of 27 lung carcinomas and one of eight breast carcinomas were found to contain mutations in codon 12. No mutations were found at position 61. Of the six possible amino acid replacements in codon 12, all but one was represented in the seven mutations identified.

Preparation and characterization of monoclonal antibodies specific for human transforming growth factor alpha.

A series of monoclonal antibodies (mAbs) against transforming growth factor alpha (TGF alpha) have been produced. The generation of these reagents, as well as their biochemical and immunochemical characterization is described. TGF alpha peptides, mutant recombinant TGF alpha proteins and two-site immunoradiometric assays were used to identify the epitopes recognized by each antibody. This approach has allowed the specific localization of immunodominant domains on the molecule. Certain mAbs were found to be useful for selected procedures. mAb 134A-2B3 was used for immunoblotting both the precursor and mature forms of TGF alpha from conditioned media of tumor cells. One mAb 189-2130.1, which reacted with the carboxyl terminal seventeen amino acids, was able to block TGF alpha binding to the EGF receptor. mAb 213-4.4 was used for immunohistochemical detection of TGF alpha in fixed tumor cells. mAbs 137-178 and 134A-2B3 were used to develop a two-site immunoradiometric immunoassay which was sensitive to 1 ng ml-1 and detected TGF alpha from a variety of tumor cells. A series of mAbs such as these could prove useful in studying the biochemical properties as well as the immunochemical localization of TGF alpha in normal tissues and tumors.

Arsenic increased lipid peroxidation in rat tissues by a mechanism independent of glutathione levels.

The role of lipid peroxidation in the mechanism of arsenic toxicity was investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione [GSH] inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were challenged with sodium arsenite, and sacrificed 1 hr after this treatment. Results showed that arsenic decreased GSH levels and increased lipid peroxidation in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8 mg/kg for lipid peroxidation induction. In the liver of rats treated with arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid peroxidation. In kidney and heart, NAC pretreatment protected the tissues against arsenic-induced depletion of GSH levels, but the same degree of protection was not found for lipid peroxidation induction. In its turn, BSO had an additive effect with arsenic in lowering the levels of GSH in the liver and kidney, but an inverse correlation between GSH levels and lipid peroxidation was found only in liver. Arsenic content in tissues of rats pretreated with NAC was lower than in rats treated only with arsenic. In rats with depleted levels of GSH (BSO-pretreated rats), a shift in arsenic tissue distribution was found, with higher levels in skin and lower levels in kidney. A clear tendency for a positive correlation between arsenic concentration and lipid peroxidation levels was found in liver, kidney, and heart.

Genotoxic monitoring of workers at a hazardous waste disposal site in Mexico.

Chromosomal aberration and sister chromatid exchange (SCE) frequencies were determined in lymphocytes cultured from 12 high-risk individuals working at a landfill for hazardous waste disposal. Cell proliferation kinetics (CPK) was also determined. Compared with 7 control individuals, no effects were observed with respect to SCE nor on CPK. However, the workers exhibited significantly higher frequencies of chromatid and chromosomal deletions, the magnitude of which was related with exposure time. This study suggests that when high-risk exposure is suspected, determining biomarkers of genotoxic damage (e.g., chromosomal aberrations), is useful for risk assessments.

Tuberculosis epidemiology and control in Veracruz, Mexico.

BACKGROUND: Tuberculosis (TB) rates remain high in regions of Southern Mexico despite the existence of a National Tuberculosis Program. Understanding TB epidemiology in such settings would assist in the design of improved TB control and highlight the challenges confronting TB control in developing countries. METHODS: We conducted a retrospective review of treatment control cards from 1991 to 1994 in five municipalities in a semiurban region of Southern Mexico. RESULTS: The relatively high rate of TB observed, 42.6 per 100,000 inhabitants, did not change significantly during the study period. Cure rates among new cases were 79% and significantly lower among retreatment cases (62%). Directly observed therapy (DOT) was administered to 84% of patients. Approximately one-half of the retreatment cases who were not cured were compliant with therapy, suggesting that drug resistance contributed to these poor results. Of particular concern was a core group of 16 patients who had received at least three treatments. CONCLUSIONS: This region of Mexico has persistently high TB rates despite a DOT-based TB control programme which achieves an overall cure rate of 77%. There exist many retreatment cases for whom cure rates are significantly lower. These cases may serve as a core group for the dissemination of drug resistant TB. The control programme is being reinforced by a nominal register of patients, decreasing administrative barriers for drug supply to individual patients and the availability of mycobacteria cultures. In addition to these measures, in regions which are approaching the levels of efficacy recommended by the WHO it may be appropriate to consider focusing efforts on the identification and treatment of chronic cases.

Day-night variations of adenosine and its metabolizing enzymes in the brain cortex of the rat--possible physiological significance for the energetic homeostasis and the sleep-wake cycle.

The role of adenosine as a metabolic regulator of physiological processes in the brain was studied by measuring its concentrations and the activity of adenosine-metabolizing enzymes: 5'-nucleotidase, S-adenosylhomocysteine hydrolase, adenosine deaminase and adenosine kinase in the cerebral cortex of the rat. Other purine compounds, such as, inosine, hypoxanthine and adenine nucleotides were also studied. The purines' pattern was bimodal with high levels of adenosine, inosine and hypoxanthine during the light period reaching their peak at 12.00 h, 08.00 h and 16.00 h, respectively, and small increments during the night between 02.00 h and 04.00 h. The enzymatic activities showed, in general, an unimodal profile with low activity during the day and high activities at night. The adenine nucleotide profile showed a significant diminution between 12.00 h and 24.00 h. The high adenosine level during the day might be due to a diminution of adenine nucleotide and to the low activity of adenosine-metabolizing enzymes, suggesting an accumulation of the nucleoside. The night increase, although of less magnitude, is simultaneous to high activity of adenosine-metabolizing enzymes and could be due to an increased formation of the nucleoside. The present data and the findings from other authors strongly suggest that adenosine in the brain cortex of the rat can participate at least in two physiological processes: regulation of the sleep-wake cycle and replenishment of the adenine nucleotide pool.

Arsenic-cadmium interaction in rats: toxic effects in the heart and tissue metal shifts.

Previously, we had shown that arsenic interacts with cadmium in rats; our results showed that the toxicity of a mixture of arsenic + cadmium cannot be predicted by the toxic mechanisms of the individual components. In this paper, we present further evidence about the interaction of arsenic and cadmium in rats. The results were: arsenic modified the 24 h-LD50 value of cadmium more clearly than cadmium did with the one of arsenic; based on the LD50 values, the mixtures we studied were more toxic than either metal alone. With single doses (As 10 mg/kg, Cd 2.6 mg/kg, and As 10 mg/kg + Cd 2.6 mg/kg) the mixture As + Cd was more toxic than each metal. At these doses, cadmium significantly induces the levels of glutathione, metallothionein, and lipid peroxidation in heart tissue, as compared to a saline group of rats. Arsenic incremented glutathione and lipid peroxidation at higher values than those obtained with cadmium. The mixture of As + Cd behaved as arsenic in the induction of lipid peroxidation and glutathione and like cadmium in metallothionein induction. Finally, rats treated with As + Cd had less Cd in liver than animals treated only with cadmium, and more As in heart tissue than rats treated only with arsenic. Our results give further evidence about the arsenic-cadmium interaction in rats, demonstrate the utility of employing different biomarkers in the study of chemical mixtures and indicate that heart tissue is affected not only by the mixture of As + Cd, but also by either metal alone.

Arsenic-cadmium interaction in rats.

Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone.

Circadian variations of adenosine level in blood and liver and its possible physiological significance.

The role of adenosine as a possible physiological modulator was explored by measuring its concentration in different tissues during a 24-hour period. Initially the circadian variations of adenosine and other purine compounds such as inosine, hypoxanthine, uric acid and adenine nucleotides were studied in the rat blood. A daily cyclic response was observed, with low levels of adenosine from 08.00 - 20.00 h, followed by an increase from this time on. Inosine and hypoxanthine levels were elevated during the day and low at night. The uric acid changes observed indicate that the decrease in purine catabolism coincides with a decrease in inosine and hypoxanthine levels and an increase in adenosine. The blood adenine nucleotides, energy charge and phosphorylation potential remained constant during the day and showed oscillatory changes during the night. Similar studies were made in the liver, a primary source of circulating purines. Liver adenosine was high during the night while inosine and hypoxanthine remained low along the 24 hours. The results suggest that liver purine metabolism might participate in the maintenance and renewal of the blood purine pool and in the energy state of erythrocytes in vivo.

Mutagenic substances in red and white wine in Chile, a high risk area for gastric cancer.

Chilean home-made and commercial wines were analyzed for the presence of mutagenic substances using the Salmonella mutagenicity test with preincubation. Strains TA98 and TA100 were used in the absence and in the presence of S9 mix. 90% of red wines from a total of 30 samples and 54% of white wines from a total of 22 were found to be mutagenic. In all cases, S9 mix did not affect the mutagenicity of the samples. At least in one case, more than one mutagen was present, since the mutagenicity with TA98 could be selectively inactivated without affecting that with TA100. This study supports the hypothesis that wine consumption may be an important risk factor for upper gastrointestinal cancer, particularly for adenocarcinoma of the stomach, which is highly prevalent in Chile.