Cytogenetic Effects Induced by Prestige Oil on Human Populations: The Role of Polymorphisms in Genes Involved in Metabolism and DNA Repair

This is a manuscript version of the article.[Abstract] The spill from the oil tanker Prestige (NW Spain, November 2002) was perhaps the biggest ecological disaster that happened worldwide in the last decades. As a consequence of this catastrophe a general concern led to a huge mobilization of human and technical resources. Given that no information was reported in the scientific literature regarding to the chronic repercussions to human health of exposure to oil spills, a pilot study was performed by our group revealing some increased genotoxic effects in the subjects exposed to the oil during cleaning activities. Due to the seriousness of the results, we extended our study comprising a larger population and including an extensive evaluation of the main polymorphic sites in metabolizing and DNA-repair genes. General increases in micronucleus (MN) frequency and decreases in the proliferation index were observed in individuals with longer time of exposure. Age was a significant predictor of MN frequency. CYP1A1 3′-UTR, EPHX1 codons 113 and 139, GSTP1, GSTM1 and GSTT1 metabolic polymorphisms, and XRCC3 codon 241 and XPD codon 751 repair polymorphisms influenced cytogenetic damage levels. In view of these results, it seems essential to pay more attention to the chronic human health effects of exposure to oil and to focus new studies on such a relevant but overlooked public health field that involves a large number of people all over the world.This work was partially funded by a grant from the Fundación Arao through the intervention of Dr. Juan Jesús Gestal and Dr. Ernesto Smyth, and by the University of A Coruña. B. Pérez-Cadahía and V. Valdiglesias were supported by fellowships from the University of A Coruña

Biomonitoring of Human Exposure to Prestige Oil: Effects on DNA and Endocrine Parameters

Since 1960, about 400 tankers spilled more than 377765 tons of oil, with the Prestige accident (Galician coast, NW Spain, November 2002) the most recent. Taking into account the consistent large number of individuals exposed to oil that exists all over the world, it seems surprising the absence in the literature of studies focused on the chronic effects of this exposure on human health. In this work we evaluated the level of DNA damage by means of comet assay, and the potential endocrine alterations (prolactin and cortisol) caused by Prestige oil exposure in a population of 180 individuals, classified in 3 groups according to the tasks performed, and 60 controls. Heavy metals in blood were determined as exposure biomarkers, obtaining significant increases of aluminum, nickel and lead in the exposed groups as compared to controls. Higher levels of genetic damage and endocrine alterations were also observed in the exposed population. DNA damage levels were influenced by age, sex, and the use of protective clothes, and prolactin concentrations by the last two factors. Surprisingly, the use of mask did not seem to protect individuals from genetic or endocrine alterations. Moreover, polymorphisms in genes encoding for the main enzymes involved in the metabolism of oil components were analyzed as susceptibility biomarkers. CYP1A1-3′UTR and EPHX1 codons 113 and 139 variant alleles were related to higher damage levels, while lower DNA damage was observed in GSTM1 and GSTT1 null individuals

Genetic Damage Induced by Accidental Environmental Pollutants

Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC), and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE), micronucleus (MN) test, and comet assay. Four groups of individuals were included: volunteers (V), hired manual workers (MW), hired high-pressure cleaner workers (HPW) and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate

Emerging roles of the mitogen and stress activated kinases MSK1 and MSK2

Mitogen- and stress-activated kinases (MSK) 1 and 2 are nuclear proteins activated downstream of the ERK1/2 or p38 MAPK pathways. MSKs phosphorylate multiple substrates, including CREB and Histone H3, and their major role is the regulation of specific subsets of Immediate Early genes (IEG). While MSKs are expressed in multiple tissues, their levels are high in immune and neuronal cells and it is in these systems most is known about their function. In immunity, MSKs have predominantly anti-inflammatory roles and help regulate production of the anti-inflammatory cytokine IL-10. In the CNS they are implicated in neuronal proliferation and synaptic plasticity. In this review we will focus on recent advances in understanding the roles of MSKs in the innate immune system and neuronal function

Influencia de determinados polimorfismos de enzimas metabólicas en la genotoxicidad del estireno

El estireno es un compuesto orgánico de gran interés comercial que se utiliza ampliamente en la manufactura de numerosos productos. La exposición a estireno se ha asociado con efectos genotóxicos, fundamentalmente tras activación metabólica a estireno-7,8-óxido (SO). El SO es detoxificado por la epóxido hidrolasa o, en menor grado, por las glutation S-transferasas. En el presente estudio se ha evaluado la influencia de los siguientes factores en la genotoxicidad del estireno: factores fisiológicos y de hábitos de vida, y polimorfismos genéticos en las mencionadas enzimas metabólicas (EPHX1 exones 3 y 4, GSTP1 exones 5 y 6, y los polimorfismos de deleción de GSTM1 y GSTT1). El diseño experimental consistió en exposición de leucocitos periféricos procedentes de 30 donantes sanos a dos dosis de SO, o a un solvente control, y evaluación de la genotoxicidad por medio del test de micronúcleos (MN) y el ensayo del cometa. Los resultados obtenidos muestran que la frecuencia de MN y el daño en el ADN inducidos por el SO se ven influenciados por la edad; sin embargo no se ha detectado influencia del consumo de tabaco, resultando poco claro el efecto del sexo. Se ha observado incremento en la longitud de la cola del cometa a medida que desciende la actividad epóxido hidrolasa en células expuestas a SO, e incremento en la frecuencia de MN en donantes de baja actividad. Estos resultados son consecuentes con la actividad detoxificadora de esta enzima. Además, se han detectado incrementos en la frecuencia de MN para los genotipos GSTP1 *A/*B y *A/*C con respecto a los homocigotos salvajes *A/*A. Esto puede deberse una baja actividad detoxificadora como consecuencia de la afinidad alterada de la proteína variante por el SO. Para los genotipos GSTM1 y GSTT1 no se obtuvieron resultados claros, incluso tras agrupar a los individuos con la misma actividad epóxido hidrolasa esperada, problablemente debido a que la conjugación con glutation juega un papel minoritario en el metabolismo del estiren