Browsing by Author "Hopenhayn, C"

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    Arsenic exposure from drinking water and birth weight
    (LIPPINCOTT WILLIAMS & WILKINS, 2003) Hopenhayn, C; Ferreccio, C; Browning, SR; Huang, B; Peralta, C; Gibb, H; Hertz Picciotto, I
    Background: Arsenic exposures front drinking water increase the risk of various cancers and noncancer health endpoints. Limited evidence suggests that arsenic may have adverse human reproductive effects. We investigated the association between drinking water arsenic exposure and fetal growth, as manifest in birth weight.
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    P53 alterations in bladder tumors from arsenic and tobacco exposed patients
    (2003) Moore, LE; Smith, AH; Eng, C; DeVries, S; Kalman, D; Bhargava, V; Chew, K; Ferreccio, C; Rey, OA; Hopenhayn, C; Biggs, ML; Bates, MN; Waldman, FM
    Previous studies demonstrated that tobacco and arsenic exposure are risk factors for bladder cancer. A case-case study was conducted to compare p53 mutations in 147 bladder tumors from South American patients by tobacco and arsenic exposure. Information on residential history and lifestyle factors was collected. The prevalence of p53 mutations and protein expression was examined in relation to tumor stage, grade, patient age, gender, tobacco and arsenic exposure. Smokers were grouped as ever/never smokers and by pack years of exposure (0, 1-20, >20). Patients were also grouped into four arsenic exposure categories based on the average of the five highest years arsenic concentration in their drinking water: group 1, non-detectable to <10 mug/l (n=50); group 2, 10-99 mug/l (n=31); group 3, 100-299 mug/l (n=35); group 4, >300 mug/l (n=30). The proportion of tumor samples with p53 mutations and P53 immunopositivity increased strongly with both stage and grade, but not with arsenic exposure or smoking. The prevalence of tumors containing mutational transitions increased markedly with tumor stage (from 14 to 52%, P-trend=0.005) and grade (from 11 to 48%, P-trend=0.004) and was higher in smokers than in non-smokers (34 versus 18%, respectively, P=0.10). An increasing trend was observed with pack years of smoking (P=0.09). The majority of mutations in tumors from both smokers and non-smokers were G-->A transitions, however, in smokers a preference for G-->A transitions at CpG sites was observed (P=0.07, two-tailed) and a positive trend was observed with pack years of exposure (P=0.04). A hotspot was found at codon 273 in 12% of the tumors from smokers but was not observed in never smokers (P=0.05) and a positive trend was observed with pack years of tobacco exposure (P=0.001). Neither stage nor grade demonstrated a preference for CpG site mutation, suggesting that these changes may be early exposure-related events in carcinogenesis and are not related to tumor progression. Arsenic exposure was not associated with an increased prevalence of p53 mutation or P53 immunopositivity and there was no evidence of interaction between arsenic and smoking with these outcome variables.
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    Profile of urinary arsenic metabolites during pregnancy
    (US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE, 2003) Hopenhayn, C; Huang, B; Christian, J; Peralta, C; Ferreccio, C; Atallah, R; Kalman, D
    Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary in-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 mug/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 mug/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not dear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus.