Browsing by Autor "Michael Levi"

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Arsenic exposure and cancer-related biomarkers in indigenous populations in Bolivia – modification by arsenic metabolism efficiency
(2024) Jessica De Loma; Noemí Tirado; Michael Levi; Jacques Gardon; Karin Bröberg
Inorganic arsenic is a known carcinogen. Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) in peripheral blood may serve as biomarkers for genotoxicity and cancer risk. Our aim is to assess if arsenic exposure influences TL and mtDNAcn in women living around Lake Poopó (Bolivia) from two ethnicities (Aymara-Quechua and Uru). Arsenic exposure was evaluated as the sum of arsenic metabolite concentrations in urine (U-As) measured by high-performance liquid chromatography online with hydride generation and inductively coupled plasma-mass spectrometry (HPLC-HG-ICP-MS), and as total arsenic in blood (B-As) measured by ICP-MS. Efficiency of arsenic metabolism was evaluated using the relative fractions of urinary metabolites, and arsenic methylating genetics (AS3MT rs3740393 and rs1046778) measured by TaqMan allelic discrimination or chip-based genotyping. TL and mtDNAcn were determined in blood by real-time PCR. Our results show that arsenic exposure (assessed as U-As and B-As) was associated with longer TL and higher mtDNAcn in this study population, and the associations were modified by arsenic metabolism capacity and AS3MT genotype.
Arsenic Exposure and Cancer-Related Proteins in Urine of Indigenous Bolivian Women
(Frontiers Media, 2020) Jessica De Loma; Anda R. Gliga; Michael Levi; Franz Ascui; Jacques Gardon; Noemí Tirado; Karin Bröberg
Indigenous people living in the Bolivian Andes are exposed through their drinking water to inorganic arsenic, a potent carcinogen. However, the health consequences of arsenic exposure in this region are unknown. The aim of this study was to evaluate associations between arsenic exposure and changes in cancer-related proteins in indigenous women (<i>n</i> = 176) from communities around the Andean Lake Poopó, Bolivia. Arsenic exposure was assessed in whole blood (B-As) and urine (as the sum of arsenic metabolites, U-As) by inductively coupled plasma-mass spectrometry (ICP-MS). Cancer-related proteins (<i>N</i> = 92) were measured in urine using the proximity extension assay. The median B-As concentration was 2.1 (range 0.60-9.1) ng/g, and U-As concentration was 67 (12-399) μg/L. Using linear regression models adjusted for age, urinary osmolality, and urinary leukocytes, we identified associations between B-As and four putative cancer-related proteins: FASLG, SEZ6L, LYPD3, and TFPI2. Increasing B-As concentrations were associated with lower protein expression of SEZ6L, LYPD3, and TFPI2, and with higher expression of FASLG in urine (no association was statistically significant after correcting for multiple comparisons). The associations were similar across groups with different arsenic metabolism efficiency, a susceptibility factor for arsenic toxicity. In conclusion, arsenic exposure in this region was associated with changes in the expression of some cancer-related proteins in urine. Future research is warranted to understand if these proteins could serve as valid biomarkers for arsenic-related toxicity.
Blood transcriptome changes linked to long-term arsenic exposure through drinking water – a cross-sectional study from the Bolivian Andes
(Elsevier BV, 2025) Ying Yang; Anastasiia Snigireva; Jessika Barrón Cuenca; Noemí Tirado; Maria Teresa Alvarez Aliaga; Gina Torres; Paolo Manghi; Philippe Gérard; Michael Levi; Jacques Gardon
Elevated arsenic exposure and efficient arsenic metabolism in indigenous women around Lake Poopó, Bolivia
(Elsevier BV, 2018) Jessica De Loma; Noemí Tirado; Franz Ascui; Michael Levi; Marie Vahter; Karin Bröberg; Jacques Gardon
Elevated concentrations of inorganic arsenic, one of the most potent environmental toxicants and carcinogens, have been detected in well water around Lake Poopó, Bolivia. This study aimed to assess human exposure to arsenic in villages around Lake Poopó, and also to elucidate whether the metabolism and detoxification of arsenic in this population is as efficient as previously indicated in other Andean areas. We recruited 201 women from 10 villages around Lake Poopó. Arsenic exposure was determined as the sum concentration of arsenic metabolites (inorganic arsenic; monomethylarsonic acid, MMA; and dimethylarsinic acid, DMA) in urine (U-As), measured by HPLC-HG-ICP-MS. Efficiency of arsenic metabolism was assessed by the relative fractions of the urinary metabolites. The women had a wide variation in U-As (range 12-407 μg/L, median 65 μg/L) and a markedly efficient metabolism of arsenic with low %MMA (median 7.7%, range: 2.2-18%) and high %DMA (80%, range: 54-91%) in urine. In multivariable-adjusted linear regression models, ethnicity (Aymara-Quechua vs. Uru), body weight, fish consumption and tobacco smoking were associated with urinary arsenic metabolite fractions. On average, the Uru women had 2.5 lower % (percentage unit) iAs, 2.2 lower %MMA and 4.7 higher %DMA compared with the Aymara-Quechua women. Our study identified several factors that may predict these women's arsenic methylation capacity, particularly ethnicity. Further studies should focus on mechanisms underlying these differences in arsenic metabolism efficiency, and its importance for the risk of arsenic-related health effects.
Increased levels of genotoxic damage in a Bolivian agricultural population exposed to mixtures of pesticides
(Elsevier BV, 2019) Jessika Barrón Cuenca; Noemí Tirado; J. Barral; Imran Ali; Michael Levi; Ulla Stenius; Marika Berglund; Kristian Dreij
During the past decades, farmers in low to middle-income countries have increased their use of pesticides, and thereby the risk of being exposed to potentially genotoxic chemicals that can cause adverse health effects. Here, the aim was to investigate the correlation between exposure to pesticides and genotoxic damage in a Bolivian agricultural population. Genotoxic effects were assessed in peripheral blood samples by comet and micronucleus (MN) assays, and exposure levels by measurements of 10 urinary pesticide metabolites. Genetic susceptibility was assessed by determination of null frequency of GSTM1 and GSTT1 genotypes. The results showed higher MN frequency in women and farmers active ≥8 years compared to their counterpart (P < 0.05). In addition, age, GST genotype, alcohol consumption, and type of water source influenced levels of genotoxic damage. Individuals with high exposure to tebuconazole, 2,4-D, or cyfluthrin displayed increased levels of genotoxic damage (P < 0.05-0.001). Logistic regression was conducted to evaluate associations between pesticide exposure and risk of genotoxic damage. After adjustment for confounders, a significant increased risk of DNA strand breaks was found for high exposure to 2,4-D, odds ratio (OR) = 1.99 (P < 0.05). In contrast, high exposure to pyrethroids was associated with a reduced risk of DNA strand breaks, OR = 0.49 (P < 0.05). It was also found that high exposure to certain mixtures of pesticides (containing mainly 2,4-D or cyfluthrin) was significantly associated with increased level and risk of genotoxic damage (P < 0.05). In conclusion, our data show that high exposure levels to some pesticides is associated with an increased risk of genotoxic damage among Bolivian farmers, suggesting that their use should be better controlled or limited.