title: Ex vivo study for the assessment of behavioral factor and gene polymorphisms in individual susceptibility to oxidative DNA damage metals-induced.
abstract: Transition metals in fine particulate matter generated by combustion induce oxidative DNA damage and inflammation. However, there is remarkable inter-individual variability in susceptibility to these damages. To assess this variability, an ex vivo study was performed using lymphocytes of 47 Caucasian healthy subjects. Cell samples were exposed to a water solution of oil fly ash (OFA). This was formed by the distinctive transition metals vanadium, iron, and nickel. Oxidative DNA damage was evaluated by testing cell viability, intracellular ROS production and 8-oxo-dG. DNA fragmentation and DNA repair capacity were assessed by using the Alkaline-Halo assay. GSTM1, GSTT1, hOGG1, and C677T and A1298C MTHFR gene polymorphisms were tested. Demographic and behavioral factors, collected by questionnaire, were also considered. OFA induced damages showed: (a) a 20-fold variation in range among different subjects in ROS production, (b) a 7-fold variation in range of 8-oxo-dG, and (c) a 25-fold variation in range in DNA repair capacity. A significant increase in DNA damage was detected in GSTT1-deficent subjects compared with wild type genotype carriers. Increases in cytoplasmic ROS and decreases in DNA repair capacity (P<0.05) were observed in C677T and A1298C variants of MTHFR. A remarkable protective effect of high fruits and vegetable intake was observed for ROS production and DNA damage. Conversely, an adverse effect of meat intake was observed on ROS increase, DNA damage and repair capacity, probably due to the increased intake of bioavailable iron. Smoking decreased DNA repair capacity, while age increased OFA-induced DNA damage. The wide comparative analysis of the complex interactions network, between genetic and behavioral factors provides evidence of the remarkable role of several lifestyle factors. In comparison to genetic polymorphisms they seem to have a higher weight in determining individual susceptibility to the adverse effects of airborne pollutants as transition metals.
authors.affiliation: Department of Hygiene, Public Health and Preventive Medicine, University of Messina, I-98100 Messina, Italy. angeladipietr@unime.it
authors.forename: Angela
authors.initials: A
authors.lastname: Di Pietro
authors.forename: Barbara
authors.initials: B
authors.lastname: Baluce
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Visalli
authors.forename: Sebastiano
authors.initials: S
authors.lastname: La Maestra
authors.forename: Rosanna
authors.initials: R
authors.lastname: Micale
authors.forename: Alberto
authors.initials: A
authors.lastname: Izzotti
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000367:Age Factors; D060729:Coal Ash / Q000737:chemistry; D003593:Cytoplasm; D004249:DNA Damage; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000235:genetics; D004032:Diet; D004781:Environmental Exposure / Q000009:adverse effects; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015438:Health Behavior; D006801:Humans; D008019:Life Style; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D019216:Metals, Heavy / Q000009:adverse effects*; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking; D055815:Young Adult
chemical_list: D060729:Coal Ash; D004785:Environmental Pollutants; D019216:Metals, Heavy; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine