title: The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes.
abstract: Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this study, we investigated the association of genomic hypomethylation with age, cigarette use, drinking status and the presence of centromere positive micronuclei (MNC+)-a biomarker for age-dependent genomic instability. Genomic hypomethylation of the repetitive element LINE-1 was measured in WBC DNA from 32 healthy male volunteers using the pyrosequencing assay. We also measured MNC+ with the micronucleus-centromere assay using a pan-centromeric probe. Possibly due to the small sample size and resulting low statistical power, smoking and drinking status had no significant effect on LINE-1 hypomethylation or the occurrence of MNC+. Consequently, we did not include them in further analyses. In contrast, LINE-1 hypomethylation and age significantly predicted MNC+; therefore, we examined whether LINE-1 hypomethylation plays a role in MNC+ formation by age, since genomic hypomethylation is associated with genomic instability. However, LINE-1 hypomethylation did not significantly mediate the effect of age on MNC+. Our data indicate that the repetitive element LINE-1 is demethylated with age and increasing MNC+ frequency, but additional studies are needed to fully understand the relation between genomic DNA hypomethylation, age and genomic instability.
authors.affiliation: Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, The University of Montana, Missoula, Montana, United States of America.
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
authors.forename: Hae Dong
authors.initials: HD
authors.lastname: Woo
authors.affiliation: Department of Psychology, The University of Montana, Missoula, Montana, United States of America.
authors.forename: Yoonhee
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, The University of Montana, Missoula, Montana, United States of America.
authors.forename: Virginia
authors.initials: V
authors.lastname: Porter
authors.affiliation: Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, The University of Montana, Missoula, Montana, United States of America.
authors.forename: Sonja
authors.initials: S
authors.lastname: Christensen
authors.affiliation: Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, The University of Montana, Missoula, Montana, United States of America.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Hamilton
authors.affiliation: Department of Molecular Epidemiology, School of Public Health, Seoul National University, Gwanak-gu, Seoul, Korea.
authors.forename: Hai Won
authors.initials: HW
authors.lastname: Chung
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D000428:Alcohol Drinking; D002467:Cell Nucleus / Q000235:genetics; D002503:Centromere / Q000235:genetics*; D019175:DNA Methylation; D042822:Genomic Instability; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012907:Smoking