title: Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis.
abstract: Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate libraries of genomic DNA fragments containing oxidatively modified bases by using specific monoclonal antibodies to immunoprecipitate enzyme-digested genome DNA. We applied this technique to two different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein-Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model. Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and mapped to each chromosome. The results revealed that distribution of the two modified bases was not random but differed in terms of chromosomes, gene size, and expression, which could be partially explained by chromosomal territory. In the wild-type mice, low GC content areas were more likely to harbor the two modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine, increased the amounts of acrolein-Ade as determined by quantitative polymerase chain reaction analyses. This versatile technique would introduce a novel research area as a high-throughput screening method for critical genomic loci under oxidative stress.
authors.affiliation: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Akatsuka
authors.forename: Than Tin
authors.initials: TT
authors.lastname: Aung
authors.forename: Khokon Kumar
authors.initials: KK
authors.lastname: Dutta
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Lee
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Liu
authors.forename: Janice
authors.initials: J
authors.lastname: Onuki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirase
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Ochi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tominaga
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Sakumi
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Kawai
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
authors.forename: Aiichi
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
mesh_terms: D000171:Acrolein / Q000737:chemistry; D000225:Adenine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics; D015870:Gene Expression; D015723:Gene Library; D052138:Genes, Neoplasm / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000276:immunology; D047468:Immunoprecipitation; D007668:Kidney / Q000737:chemistry; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: C514955:1,N6-propanoadenine; D000911:Antibodies, Monoclonal; C024829:8-hydroxyguanine; D006147:Guanine; D000171:Acrolein; D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D000225:Adenine