The response to oxidative stress and metallomics analysis in a twin study: The role of the environment.
Inefficient response to oxidative stress has been associated with ageing and health risk. Metals are known to inhibit DNA repair and may modify the antioxidant response. How genetic variability and lifestyle factors modulate the response to oxidative stress is poorly explored. Our study aims to disentangle the contribution of genetics and environmental exposures to oxidative stress response using data from twin pairs. The non-enzymatic antioxidant capacity (NEAC), the repair capacity of 8-oxo-7,8-dihydroguanine (OGG activity) and the levels of 12 metals were measured in blood of 64 monozygotic and 31 dizygotic twin pairs. The contributions of genetic and environmental effects were assessed using standard univariate twin modelling. NEAC and OGG activity significantly decreased with age. Gender-, age- and body mass index-associated differences were identified for some metals. Principal Component Analysis identified two groups of metals whose levels in blood were highly correlated: As, Hg, Pb, Se, Zn and Al, Co, Cr, Mn, Ni. The environmental influence was predominant on OGG activity and NEAC variance whereas for most metals the best-fitting model incorporated additive genetic and unique environmental sources of variance. NEAC and OGG activity were both inversely correlated with blood levels of various metals. The inhibition of OGG activity by Cd was largely explained by smoking. Our data show a substantial role of environmental factors in NEAC and OGG activity variance that is not explained by twins' age. Exogenous environmental factors such as metals contribute to oxidative stress by decreasing NEAC and inhibiting repair of oxidatively-induced DNA damage.
National Center of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.
Emanuela
E
Medda
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Anna
A
Minoprio
National Center of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.
Lorenza
L
Nisticò
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Beatrice
B
Bocca
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Valeria
V
Simonelli
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Mariarosaria
M
D'Errico
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Angelo
A
Calcagnile
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Alessandro
A
Giuliani
National Center of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.
Virgilia
V
Toccaceli
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Luisa
L
Minghetti
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Alessandro
A
Alimonti
National Center of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.
Maria Antonietta
MA
Stazi
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy. Electronic address: filomena.mazzei@iss.it.
Filomena
F
Mazzei
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy. Electronic address: eugenia.dogliotti@iss.it.
Eugenia
E
Dogliotti
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D004249:DNA Damage; D045647:DNA Glycosylases / Q000097:blood; D004260:DNA Repair; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D019216:Metals, Heavy / Q000097:blood; D018384:Oxidative Stress; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
D000975:Antioxidants; D015415:Biomarkers; D004785:Environmental Pollutants; D019216:Metals, Heavy; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human
8-Oxoguanine DNA glycosylase; Antioxidant capacity; DNA repair; Metals; Twins