title: DNA damage response in monozygotic twins discordant for smoking habits.
abstract: Previous studies in twins indicate that non-shared environment, beyond genetic factors, contributes substantially to individual variation in mutagen sensitivity; however, the role of specific causative factors (e.g. tobacco smoke, diet) was not elucidated. In this investigation, a population of 22 couples of monozygotic twins with discordant smoking habits was selected with the aim of evaluating the influence of tobacco smoke on individual response to DNA damage. The study design virtually eliminated the contribution of genetic heterogeneity to the intra-pair variation in DNA damage response, and thus any difference in the end-points investigated could directly be attributed to the non-shared environment experienced by co-twins, which included as main factor cigarette smoke exposure. Peripheral lymphocytes of study subjects were challenged ex vivo with γ-rays, and the induction, processing, fixation of DNA damage evaluated through multiple approaches. Folate status of study subjects was considered significant covariate since it is affected by smoking habits and can influence radiosensitivity. Similar responses were elicited by γ-rays in co-twins for all the end-points analysed, despite their discordant smoking habits. Folate status did not modify DNA damage response, even though a combined effect of smoking habits, low-plasma folic acid level, and ionising radiation was observed on apoptosis. A possible modulation of DNA damage response by duration and intensity of tobacco smoke exposure was suggested by Comet assay and micronucleus data, but the effect was quantitatively limited. Overall, the results obtained indicate that differences in smoking habits do not contribute to a large extent to inter-individual variability in the response to radiation-induced DNA damage observed in healthy human populations.
authors.affiliation: Department of Environment and Primary Prevention, Istituto Superiore diSanità, V.le Regina Elena 299, 00161 Rome, Italy. francesca.marcon@iss.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Marcon
authors.forename: Daniela
authors.initials: D
authors.lastname: Carotti
authors.forename: Cristina
authors.initials: C
authors.lastname: Andreoli
authors.forename: Ester
authors.initials: E
authors.lastname: Siniscalchi
authors.forename: Paola
authors.initials: P
authors.lastname: Leopardi
authors.forename: Stefania
authors.initials: S
authors.lastname: Caiola
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Zijno
authors.forename: Emanuela
authors.initials: E
authors.lastname: Medda
authors.forename: Lorenza
authors.initials: L
authors.lastname: Nisticò
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Crebelli
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D020552:Comet Assay; D003430:Cross-Sectional Studies; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects; D023381:Endpoint Determination; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000097:blood; D005720:Gamma Rays; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007700:Kinetics; D016014:Linear Models; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D010766:Phosphorylation; D011836:Radiation Tolerance; D012907:Smoking / Q000009:adverse effects*; D014430:Twins, Monozygotic; D014805:Vitamin B 12 / Q000097:blood
chemical_list: C468783:H2AX protein, human; D006657:Histones; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12