Diminished Anthropometric Measures and Other Associated Variables in a Sample of Violent Offenders: A Case-Control Study.

Background Predicting criminal behavior is a complex task due to its multidimensional nature. Nevertheless, health professionals and criminologists must consider individual criminogenic risk factors to provide reliable expert opinions. Physical traits have been a subject of scrutiny since the inception of biological positivism. Aim The main objective of this study is to analyze differences in individual characteristics between violent offenders and healthy volunteers to potentially identify predictors of criminal behavior. Methods We conducted a case-control study with a sample of inmates convicted of violent offenses and compared them to healthy volunteers. Anthropometrics, sociodemographic data, drug consumption, characteristics of the family nucleus, clinical background, and basic laboratory test results were collected. Quantitative data were tested for normality and homogeneity before applying the Mann-Whitney or T-Student tests, respectively. For categorical data, Pearson's chi-square test was used for associations, and the odds ratio was determined for the associated risk in drug abuse profiles. Results Among the male participants (N = 72), the inmate group (n = 41) showed significantly lower stature (mean height [m]: 1.7454 ± 0.0694 vs 1.6643 ± 0.0659, p < 0.001), a reduced left D2:D4 finger length ratio (mean ratio [cm]: 0.9638 ± 0.0572 vs 0.9380 ± 0.068cm, p < 0.05), and smaller anthropometric measurements, including armful (mean length [m]: 1.8080 ± 0.7690 vs 1.6582 ± 0.7250, p < 0.001), wrist (mean [cm]: 17.39 ± 1.10 vs 16.57 ± 1.84, p < 0.05), mid-upper arm (mean [cm]: 31.75 ± 3.79 vs 29.97 ± 3.79, p < 0.05), and head circumferences (mean [cm]: 58.43 ± 1.92 vs 55.39 ± 1.51, p < 0.001). Additionally, the inmate group exhibited shorter lower segments (mean [cm]: 102.67 ± 4.97 vs. 97.85 ± 5.04, p < 0.001) and plantar lengths (mean [cm]: 27.45 ± 1.25 vs. 26.78 ± 1.00, p < 0.05). Furthermore, this group displayed a higher risk of alcohol (OR = 4.4, p < 0.01), cocaine (OR = 3.36, p < 0.05), and benzodiazepine consumption (OR = 3.36, p < 0.05). Parental alcohol consumption (χ² = 12.66, p < 0.01) and the practice of Protestantism (χ² = 20.087, p < 0.001) were also associated with the inmate group. Conclusion Physical traits may be considered potential criminogenic risk factors, but larger studies are necessary to validate these findings. Future research should take into account physiological and psychological correlates to gain a comprehensive understanding of the complex relationship between physical traits and criminal behavior.

Abnormal expression of H-Ras induces S-phase arrest and mitotic catastrophe in human T-lymphocyte leukemia.

Background: Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and paradoxically, initiation of cell death. Methods: This study investigated the effect of H-Ras expression on human T-cell acute lymphoblastic leukemia MOLT-4 cells. Cells were electroporated with either wild-type (Raswt) or oncogenic mutant in codon 12 exon 1 (Rasmut) versions of H-Ras gene and stained for morphological analysis. Cell viability was assessed using trypan blue staining and cell cycle analysis using flow cytometry. H-Ras gene expression was determined using quantitative real-time reverse transcription polymerase chain reaction. The t, ANOVA, and Scheffe tests were used for statistical analysis. Results: Human T-cell acute lymphoblastic leukemia MOLT-4 cells showed nuclear fragmentation and presence of multiple nuclei and micronuclei after transfection with either wt or mutant H-Ras genes. Cell cycle analysis revealed a statistically significant increase in cells in the S phase when transfected with either wt (83.67%, P<0.0005) or mutated (81.79%, P<0.0001) H-Ras genes. Although similar effects for both versions of H-Ras were found, cells transfected with the mutated version died at 120 h of mitotic catastrophe. Conclusion: Transfection of human T-cell acute lymphoblastic leukemia MOLT-4 cells with either normal or mutated H-Ras genes induced alterations in morphology, arrest in the S phase, and death by mitotic catastrophe.

Frequency of non-alcoholic fatty liver disease in a series of forensic cases in Mexico / Frecuencia de hígado graso no alcohólico en una serie de casos forenses en México

Abstract Objective: To determine the frequency of non-alcoholic fatty liver in individuals with not known history of liver disease, who died instantly in a traffic accident. Materials and Methods: It was a prospective and cross-sectional study of a series of autopsy cases, with a convenience sample obtained from the forensic medical service in the municipality of Boca del Río, Mexico, during the period from January to December 2016. The variables studied included age, sex, weight, height, abdominal circumference, thickness of the adipose panicle, cause of death and findings of liver biopsy. Results: A 78.1% of the 32 cases studied were men. The average age was 48 years old (range 20-80 years old). The body mass index range was 17-33. 34% of the cases had fatty liver. 27.3% of cases with fatty liver had a normal body mass index. Conclusions: This postmortem study showed a higher frequency of asymptomatic hepatic steatosis than previously reported in the Mexican population. It is necessary to establish timely national measures to detect and to prevent complications of this disease.

Resumen Objetivo: Determinar la frecuencia de hígado graso no alcohólico en individuos sin antecedentes conocidos de enfermedad hepática, que murieron instantáneamente en un accidente de tráfico. Materiales y Métodos: Fue un estudio prospectivo y transversal, de una serie de casos de autopsia, con una muestra por conveniencia obtenida en el servicio médico forense en el municipio de Boca del Río, México, durante el período de enero a diciembre de 2016. Las variables estudiadas incluyeron edad, sexo, peso, altura, perímetro abdominal, grosor del panículo adiposo, causa de muerte y hallazgos de la biopsia hepática. Resultados: De los 32 casos estudiados, el 78,1% eran hombres. La edad promedio fue de 48 años (rango 20-80 años). El rango del índice de masa corporal fue de 17-33. Un 34% de los casos tenían hígado graso. El 27.3% de los casos con hígado graso tenían un índice de masa corporal normal. Conclusiones: Este estudio postmortem mostró una frecuencia más alta de esteatosis hepática asintomática que la reportada previamente en la población mexicana. Es necesario establecer medidas nacionales oportunas para detectar y prevenir complicaciones de esta enfermedad.

Nuclear abnormalities in umbilical cord blood lymphocytes of newborns from the Ahome and Guasave municipalities in Sinaloa, Mexico.

AIM: We measured the frequency of nuclear abnormalities of 210 blood samples from the umbilical cord, since human fetuses are exposed to environmental mixtures of pesticides that induce DNA damage. METHODS: The determinations were made through the micronucleus assay test in lymphocytes from the umbilical cord blood of newborns whose mothers live in Ahome (n = 105) and Guasave (n = 105), Sinaloa, Mexico. RESULTS: The average frequency of anomalies in 1000 cells were, respectively: micronucleus 0.4 vs. 2.9, pyknotic cells 18.3 vs. 109.2, chromatin condensation 7.7 vs. 150.1, karyolitic cells 1.8 vs. 24.4, and binucleated cells 4.9 vs. 74.6. The calculated Pearson correlation factors of nuclear abnormality frequencies between both municipalities were low and negative, suggesting that they did not correlate between the Ahome and Guasave newborns and indicating a higher number of mothers exposed in Guasave. CONCLUSION: Our data suggest that monitoring nuclear abnormalities in umbilical cord blood samples could be a useful tool to identify transplacental mutagens perfusion that is being discharged into the local environment.

Sudden Death Report in Mexico (1998-2014).

Introduction: Sudden death (SD) is a health problem worldwide affecting all strata of the population. The main cause of SD is ischemic heart disease (IHD). The aims of the study were as follows: (i) to analyze the incidence of deaths from IHD in two successive periods (1998-2006 and 2007-2015) to visualize the magnitude of the problem and (ii) to review the official reports of SD in the same lapse of time. Materials and Methods: During that period, instantaneous death (ISD) and death that occurred in the first 24 h after the onset of symptoms were analyzed according to the official databases of National Institute of Statistics and Geography (INEGI) and National Health Information System (SINAIS). Results: There was an under-registration of SD cases in Mexico. Only 1394 cases of ISD were recorded officially in 17 years period of study, whereas it is estimated that 33,000 cases occur annually, exclusively due to sudden cardiac death. Conclusion: There is a serious gap in the official epidemiological information; placing the real problem in perspective would help to establish the adequate public policies for both, prevention and investigation of the causes of SD in Mexico.

Introducción: La muerte súbita (MS) es un problema mundial de salud que afecta a todos los estratos de la población. La principal causa de MS es la cardiopatía isquémica. Los objetivos del estudio fueron: i) Analizar la incidencia de muertes por cardiopatía isquémica en dos períodos sucesivos (1998-2006 y 2007-2015) para visualizar la magnitud del problema, y ii) revisar los informes oficiales de MS en los mismos lapsos. Metodología: Durante ese período, se analizaron la muerte instantánea (MSI) y la muerte ocurrida en las primeras 24 h después del inicio de los síntomas (MS24h) de acuerdo con las bases de datos oficiales del Instituto Nacional de Estadística y Geografía (INEGI) y el Sistema Nacional de Información de Salud (SINAIS). Resultados: Existe un subregistro de casos de MS en México. Solo 1,394 casos de MSI se registraron oficialmente en el período de estudio de 17 años, mientras que se estima que ocurren 33,000 casos al año, solo por muerte súbita cardíaca. Conclusión: Existe una subregistro de información epidemiológica oficial; poner el problema real en perspectiva ayudaría a establecer políticas públicas adecuadas tanto para la prevención como para la investigación de las causas de la MS en México.

Sudden Death Report in Mexico (1998-2014).

Introduction: Sudden death (SD) is a health problem worldwide affecting all strata of the population. The main cause of SD is ischemic heart disease (IHD). The aims of the study were as follows: (i) to analyze the incidence of deaths from IHD in two successive periods (1998-2006 and 2007-2015) to visualize the magnitude of the problem and (ii) to review the official reports of SD in the same lapse of time. Materials and Methods: During that period, instantaneous death (ISD) and death that occurred in the first 24 h after the onset of symptoms were analyzed according to the official databases of National Institute of Statistics and Geography (INEGI) and National Health Information System (SINAIS). Results: There was an under-registration of SD cases in Mexico. Only 1394 cases of ISD were recorded officially in 17 years period of study, whereas it is estimated that 33,000 cases occur annually, exclusively due to sudden cardiac death. Conclusion: There is a serious gap in the official epidemiological information; placing the real problem in perspective would help to establish the adequate public policies for both, prevention and investigation of the causes of SD in Mexico.

Introducción: La muerte súbita (MS) es un problema mundial de salud que afecta a todos los estratos de la población. La principal causa de MS es la cardiopatía isquémica. Los objetivos del estudio fueron: i) Analizar la incidencia de muertes por cardiopatía isquémica en dos períodos sucesivos (1998-2006 y 2007-2015) para visualizar la magnitud del problema, y ii) revisar los informes oficiales de MS en los mismos lapsos. Metodología: Durante ese período, se analizaron la muerte instantánea (MSI) y la muerte ocurrida en las primeras 24 h después del inicio de los síntomas (MS24h) de acuerdo con las bases de datos oficiales del Instituto Nacional de Estadística y Geografía (INEGI) y el Sistema Nacional de Información de Salud (SINAIS). Resultados: Existe un subregistro de casos de MS en México. Solo 1,394 casos de MSI se registraron oficialmente en el período de estudio de 17 años, mientras que se estima que ocurren 33,000 casos al año, solo por muerte súbita cardíaca. ­. Conclusión: Existe una subregistro de información epidemiológica oficial; poner el problema real en perspectiva ayudaría a establecer políticas públicas adecuadas tanto para la prevención como para la investigación de las causas de la MS en México.

Sudden Death Report in Mexico (1998-2014) / Reporte de muerte súbita en Mexico (1998-2014)

Abstract Introduction: Sudden death (SD) is a health problem worldwide affecting all strata of the population. The main cause of SD is ischemic heart disease (IHD). The aims of the study were as follows: (i) to analyze the incidence of deaths from IHD in two successive periods (1998-2006 and 2007-2015) to visualize the magnitude of the problem and (ii) to review the official reports of SD in the same lapse of time. Materials and Methods: During that period, instantaneous death (ISD) and death that occurred in the first 24 h after the onset of symptoms were analyzed according to the official databases of National Institute of Statistics and Geography (INEGI) and National Health Information System (SINAIS). Results: There was an under-registration of SD cases in Mexico. Only 1394 cases of ISD were recorded officially in 17 years period of study, whereas it is estimated that 33,000 cases occur annually, exclusively due to sudden cardiac death. Conclusion: There is a serious gap in the official epidemiological information; placing the real problem in perspective would help to establish the adequate public policies for both, prevention and investigation of the causes of SD in Mexico.

Resumen Introducción: La muerte súbita (MS) es un problema mundial de salud que afecta a todos los estratos de la población. La principal causa de MS es la cardiopatía isquémica. Los objetivos del estudio fueron: i) Analizar la incidencia de muertes por cardiopatía isquémica en dos períodos sucesivos (1998-2006 y 2007-2015) para visualizar la magnitud del problema, y ii) revisar los informes oficiales de MS en los mismos lapsos. Metodología: Durante ese período, se analizaron la muerte instantánea (MSI) y la muerte ocurrida en las primeras 24 h después del inicio de los síntomas (MS24h) de acuerdo con las bases de datos oficiales del Instituto Nacional de Estadística y Geografía (INEGI) y el Sistema Nacional de Información de Salud (SINAIS). Resultados: Existe un subregistro de casos de MS en México. Solo 1,394 casos de MSI se registraron oficialmente en el período de estudio de 17 años, mientras que se estima que ocurren 33,000 casos al año, solo por muerte súbita cardíaca. Conclusión: Existe una subregistro de información epidemiológica oficial; poner el problema real en perspectiva ayudaría a establecer políticas públicas adecuadas tanto para la prevención como para la investigación de las causas de la MS en México.

Non-Phosphorylated Tau in Cerebrospinal Fluid is a Marker of Alzheimer's Disease Continuum in Young Urbanites Exposed to Air Pollution.

Long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above USEPA standards is associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) children exhibit subcortical pretangles in infancy and cortical tau pre-tangles, NFTs, and amyloid phases 1-2 by the 2nd decade. Given their AD continuum, we measured in 507 normal cerebrospinal fluid (CSF) samples (MMC 354, controls 153, 12.82±6.73 y), a high affinity monoclonal non-phosphorylated tau antibody (non-P-Tau), as a potential biomarker of AD and axonal damage. In 81 samples, we also measured total tau (T-Tau), tau phosphorylated at threonine 181 (P-Tau), amyloid-ß1-42, BDNF, and vitamin D. We documented by electron microscopy myelinated axonal size and the pathology associated with combustion-derived nanoparticles (CDNPs) in anterior cingulate cortex white matter in 6 young residents (16.25±3.34 y). Non-P-Tau showed a strong increase with age significantly faster among MMC versus controls (p = 0.0055). Aß1 - 42 and BDNF concentrations were lower in MMC children (p = 0.002 and 0.03, respectively). Anterior cingulate cortex showed a significant decrease (p = <0.0001) in the average axonal size and CDNPs were associated with organelle pathology. Significant age increases in non-P-Tau support tau changes early in a population with axonal pathology and evolving AD hallmarks in the first two decades of life. Non-P-Tau is an early biomarker of axonal damage and potentially valuable to monitor progressive longitudinal changes along with AD multianalyte classical CSF markers. Neuroprotection of young urbanites with PM2.5 and CDNPs exposures ought to be a public health priority to halt the development of AD in the first two decades of life.

Time trend tendency (1988-2014 years) of organochlorine pesticide levels in the adipose tissue of Veracruz inhabitants.

The population that lives in areas where organochlorine pesticides were spread in the past is still exposed to them through contaminated food, particulate matter, and vapors. Due to their lipophilic properties and resistance to metabolic reactions, they accumulate in tissues and fluids rich in lipids. The aim of the study was to monitor the concentrations of organochlorine pesticides in forensic adipose tissue samples of adult inhabitants of Veracruz City, Mexico, and compare their time trend levels from 1988 to 2014. During the study, hexachlorobenzene (HCB); lindane; ß-hexachorocyclohexane; p,p'-dichlorodiphenyldichloroethylene (pp'DDE); p,p'-dichlorodiphenyldichloroethane (p,p'-DDT); and o,p'-dichlorodiphenyldichloroethane (o,p'-DDT) were determined. Our survey was divided into two periods: first, from the years 1988 to 1999, during which DDT was allowed to fight malaria and dengue vectors and the second from the years 2001 to 2014, after the DDT ban. A total of 1435 samples were analyzed. There were substantial differences in the forecasted time trend values of p,p'-DDE and p,p'-DDT in human adipose tissue samples in the two different periods. During the first period, p,p'-DDE decrease time trend was 1.198 mg/kg on lipid base per year; for the second one, decrease was 0.128 mg/kg on lipid base per year. p,p'-DDT decreased 0.507 mg/kg on lipid base during the first period and 0.039 mg/kg on lipid base for the second. The different concentrations may be explained by the cessation of fresh exposure after the first period and a more equilibrated decontamination tendency during the second period. This model was useful to show the decrease in the concentration of pesticides in human adipose tissue samples.

Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.

Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-ß (Aß)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), Aß1-42, α-synuclein (t-α-syn and d-α-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. Aß1-42 and BDNF concentrations were significantly lower in MCMA children versus controls (p = 0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 µg/m3 and then decreased, regardless of cumulative value or age (R2 = 0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-α-synuclein showed a significant correlation with TNFα, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R2 = 0.47), while d-α-synuclein exhibited a tendency to increase with cumulated PM2.5 (R2 = 0.30). CSF Aß1-42, BDNF, α-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority.

YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

BACKGROUND AND AIMS: Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. METHODS: There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). RESULTS: There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). CONCLUSIONS: YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC.

The association between first trimester micronutrient intake, MTHFR genotypes, and global DNA methylation in pregnant women.

OBJECTIVE: Our aim was to evaluate possible associations between consumption of micronutrients involved in one-carbon metabolism, MTHFR genotypes, and global DNA methylation in pregnant women. METHODS: A semi-quantitative dietary questionnaire was administered to 195 women during their first trimester in Morelos, Mexico. Two functional polymorphisms of the key folate-metabolizing gene, i.e. MTHFR 677 C>T and 1298 A>C, as well as global DNA methylation were assessed in peripheral blood drawn during the interview. RESULTS: Independent of maternal age and caloric intake, vitamin B(6) deficiency was associated with 1.8 fold increased risk of hypomethylation in women carrying the MTHFR 677 T allele. CONCLUSIONS: There exists a subpopulation that is more susceptible to B vitamin deficiencies.

Exposure to phthalates and breast cancer risk in northern Mexico.

BACKGROUND: Phthalates, ubiquitous environmental pollutants that may disturb the endocrine system, are used primarily as plasticizers of polyvinyl chloride and as additives in consumer and personal care products. OBJECTIVES: In this study, we examined the association between urinary concentrations of nine phthalate metabolites and breast cancer (BC) in Mexican women. METHODS: We age-matched 233 BC cases to 221 women residing in northern Mexico. Sociodemographic and reproductive characteristics were obtained by direct interviews. Phthalates were determined in urine samples (collected pretreatment from the cases) by isotope dilution/high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: Phthalate metabolites were detected in at least 82% of women. The geometric mean concentrations of monoethyl phthalate (MEP) were higher in cases than in controls (169.58 vs. 106.78 microg/g creatinine). Controls showed significantly higher concentrations of mono-n-butyl phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(3-carboxypropyl) phthalate (MCPP) than did the cases. After adjusting for risk factors and other phthalates, MEP urinary concentrations were positively associated with BC [odds ratio (OR), highest vs. lowest tertile = 2.20; 95% confidence interval (CI), 1.33-3.63; p for trend < 0.01]. This association became stronger when estimated for premenopausal women (OR, highest vs. lowest tertile = 4.13; 95% CI, 1.60-10.70; p for trend < 0.01). In contrast, we observed significant negative associations for monobenzyl phthalate (MBzP) and MCPP. CONCLUSIONS: We show for the first time that exposure to diethyl phthalate, the parent compound of MEP, may be associated with increased risk of BC, whereas exposure to the parent phthalates of MBzP and MCPP might be negatively associated. These findings require confirmation.

Sodium arsenite alters cell cycle and MTHFR, MT1/2, and c-Myc protein levels in MCF-7 cells.

There is limited available information on the effects of arsenic on enzymes participating in the folate cycle. Therefore, our aim was to evaluate the effects of sodium arsenite on the protein levels of methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) and its further relationship with the expression MT1/2 and c-myc in MCF-7 cells. Arsenite treatment (0-10 microM) for 4 h decreased MTHFR levels in a concentration-dependent fashion without significant effects on DHFR. The effects on MTHFR were observed at arsenite concentrations not significantly affecting cell viability. We also observed an increase in S-phase recruitment at all concentrations probed. Lower concentrations (<5 microM) induced cell proliferation, showing a high proportion of BrdU-stained cells, indicating a higher DNA synthesis rate. However, higher concentrations (> or =5 microM) or longer treatment periods induced apoptosis. Arsenite also induced dose-dependent increases in MT1/2 and c-Myc protein levels. The levels of MTHFR were inversely correlated to MT1/2 and c-Myc overexpression and increased S-phase recruitment. Our findings indicate that breast epithelial cells are responsive to arsenite and suggest that exposure may pose a risk for breast cancer. The reductions in MTHFR protein levels contribute to understand the mechanisms underlying the induction of genes influencing growth regulation, such as c-myc and MT1/2. However, further research is needed to ascertain if the effects here reported following short-time and high-dose exposure are relevant for human populations chronically exposed to low arsenic concentrations.

Biomarkers of oxidative stress and damage in human populations exposed to arsenic.

Arsenic (As) is an ubiquitous element in the environment for which the main route of human exposure is through consumption of drinking water. Reactive oxygen species generation (ROS) associated with As exposure is known to play a fundamental role in the induction of adverse health effects and disease (cancer, diabetes, hypertension, and cardiovascular and neurological diseases). However, the precise mechanisms of oxidative stress and damage from As exposure are not fully understood and moreover the use of non-invasive methods of measuring ROS generation and oxidative damage footprints in humans is no easy task. Although As induces adverse health effects not all exposed individuals develop degenerative chronic diseases or even manifest adverse effects or symptoms, suggesting that genetic susceptibility is an important factor involved in the human response to As exposure. This mini-review summarizes the literature describing the molecular mechanisms affected by As, as well as the most used biomarkers of oxidative stress and damage in human populations. The most reported biomarkers of oxidative DNA damage are the urinary excretion of 8-OHdG and the comet assay in lymphocytes, and more recently DNA repair mechanism markers from the base and nuclear excision repair pathways (BER and NER). Genetic heterogeneity in the oxidative stress pathways involved in As metabolism are important causative factors of disease. Thus further refinement of human exposure assessment is needed to reinforce study design to evaluate exposure-response relationships and study gene-environment interactions. The use of microarray-based gene expression analysis can provide better insights of the underlying mechanisms involved in As-induced diseases and could help to identify target genes that can be modulated to prevent disease.

Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-kappaB activation and cell proliferation in human breast cancer MCF-7 cells.

Epidemiological evidence has associated exposure to arsenic (As) in drinking water with an increased incidence of human cancers in the skin, bladder, liver, kidney and lung. Sodium arsenite mimics the effects of estradiol and induces cell proliferation in the estrogen responsive breast cancer cell line MCF-7. Therefore, our aim was to further explore the ability of sodium arsenite to induce MCF-7 epithelial breast cell proliferation and some of its underlying mechanisms by studying ROS production, c-Myc and HO-1 protein levels, 8-OHdG formation and NF-kappaB activation. Low arsenite concentrations (0.5-5 microM) induced ROS production and ROS-related depolarization of the mitochondrial membrane suggesting that mitochondria played an important role in the oxidative effects of As. ROS-mediated DNA damage as measured by the presence of 8-OHdG DNA-adducts in their nuclei, IkappaB phosphorylation, NF-kappaB activation and increases in c-Myc and HO-1 protein levels were also observed, suggesting that these factors play a relevant role in the arsenite induced MCF-7 cell recruitment into the S-phase of the cell cycle and cell proliferation observed. In conclusion, arsenite activates several pathways involved in MCF-7 cell proliferation suggesting that arsenite exposure may pose a risk for breast cancer in human exposed populations notwithstanding that most studies to date have not yet implicated this metalloid as a cofactor in the etiology of this disease.

Benzoquinone activates the ERK/MAPK signaling pathway via ROS production in HL-60 cells.

Benzene (BZ) is a class I carcinogen and its oxidation to reactive intermediates is a prerequisite of hematoxicity and myelotoxicity. The generated metabolites include hydroquinone, which is further oxidized to the highly reactive 1,4-benzoquinone (BQ) in bone marrow. Therefore, we explored the mechanisms underlying BQ-induced HL-60 cell proliferation by studying the role of BQ-induced reactive oxygen species (ROS) in the activation of the ERK-MAPK signaling pathway. BQ treatment (0.01-30 microM) showed that doses below 10 microM did not significantly reduce viability. ROS production after 3 microM BQ treatment increased threefold; however, catalase addition reduced ROS generation to basal levels. FACS analysis showed that BQ induced a fivefold increase in the proportion of cells in S-phase. We also observed a high proportion of Bromodeoxyuridine (BrdU) stained cells, indicating a higher DNA synthesis rate. BQ also produced rapid and prolonged phosphorylation of ERK1/2 proteins. Simultaneous treatment with catalase or PD98059, a potent MEK protein inhibitor, reduced cell recruitment into the S-phase and also abolished the ERK1/2 protein phosphorylation induced by BQ, suggesting that MEK/ERK is an important pathway involved in BQ-induced ROS mediated proliferation. The prolonged activation of ERK1/2 contributes to explain the increased S-phase cell recruitment and to understand the leukemogenic processes associated with exposure to benzene metabolites. Thus, the possible mechanism by which BQ induce HL-60 cells to enter the cell cycle and proliferate is linked to ROS production and its growth promoting effects by specific activation of regulating genes known to be activated by redox mechanisms.