研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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The role of oxidative DNA damage in human arsenic carcinogenesis: Detection of 8-hydroxy-2 '-deoxyguanosine in arsenic-related Bowen's disease

Matsui M, Nishigori C, Toyokuni S, Takada J, Akaboshi M, Ishikawa M, Imamura S, Miyachi Y

JOURNAL OF INVESTIGATIVE DERMATOLOGY 113 巻 ( 1 ) 頁： 26 - 31 1999年7月

The role of oxidative DNA damage in human arsenic carcinogenesis: Detection of 8-hydroxy-2 '-deoxyguanosine in arsenic-related Bowen's disease

Matsui M, Nishigori C, Toyokuni S, Takada J, Akaboshi M, Ishikawa M, Imamura S, Miyachi Y

JOURNAL OF INVESTIGATIVE DERMATOLOGY 113 巻 ( 1 ) 頁： 26 - 31 1999年7月

High incidence of allelic loss on chromosome 5 and inactivation of p15(INK4B) and p16(INK4A) tumor suppressor genes in oxystress-induced renal cell carcinoma of rats

Tanaka T, Iwasa Y, Kondo S, Hiai H, Toyokuni S

ONCOGENE 18 巻 ( 25 ) 頁： 3793 - 3797 1999年6月

High incidence of allelic loss on chromosome 5 and inactivation of p15(INK4B) and p16(INK4A) tumor suppressor genes in oxystress-induced renal cell carcinoma of rats

Tanaka T., Iwasa Y., Kondo S., Hiai H., Toyokuni S.

Oncogene 18 巻 ( 25 ) 頁： 3793 - 3797 1999年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Oncogene

Ferric nitrilotriacetate induces oxidative damage in renal proximal tubules, a consequence of Fenton-like reaction, that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. In order to find common genetic alterations in this oxystress-induced carcinogengesis model, RCCs were produced in F1 hybrid rats between Wistar and Long-Evans strains and genomes were screened for loss of heterozygosity (LOH) with microsatellite polymorphic markers by PCR. Five consecutive markers on chromosome 5 (D5Mgh5, D5Mit9, D5Mgh6, D5Mit11 and D5Mit6) showed LOH in ≥ 40% of the RCCs. As possible candidate tumor suppressor genes on chromosome 5, p15(INK4B) and p16(INK4A) were investigated for genetic alteration and aberrant methylation by Southern blot, PCR/SSCP/sequencing and methylation-specific PCR. Genetic alteration (homozygous or hemizygous deletion with or without point mutation) or aberrant methylation were found in 30.7 and 53.8% of the RCC cases, respectively, which was proportionally associated with the histological nuclear grade and metastatic activity. Our data suggest that inactivation of p15 and p16 genes could be one of the major pathways responsible for oxystress-induced carcinogenesis.

DOI： 10.1038/sj.onc.1202707

Scopus

High incidence of allelic loss on chromosome 5 and inactivation of p15(INK4B) and p16(INK4A) tumor suppressor genes in oxystress-induced renal cell carcinoma of rats

Tanaka T, Iwasa Y, Kondo S, Hiai H, Toyokuni S

ONCOGENE 18 巻 ( 25 ) 頁： 3793 - 3797 1999年6月

A 1-hour enzyme-linked immunosorbent assay for quantitation of acrolein- and hydroxynonenal-modified proteins by epitope-bound casein matrix method 査読有り国際誌

Satoh K, Yamada S, Koike Y, Igarashi Y, Toyokuni S, Kumano T, Takahata T, Hayakari M, Tsuchida S, Uchida K

ANALYTICAL BIOCHEMISTRY 270 巻 ( 2 ) 頁： 323 - 328 1999年6月

A 1-hour enzyme-linked immunosorbent assay for quantitation of acrolein- and hydroxynonenal-modified proteins by epitope-bound casein matrix method

Satoh K., Yamada S., Koike Y., Igarashi Y., Toyokuni S., Kumano T., Takahata T., Hayakari M., Tsuchida S., Uchida K.

Analytical Biochemistry 270 巻 ( 2 ) 頁： 323 - 328 1999年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Analytical Biochemistry

A simple and rapid enzyme-linked immunosorbent assay (ELISA) method for quantitation of acrolein and 4-hydroxy-2-nonenal (HNE)-modified proteins was developed. Microtiter plate wells were precoated and blocked simultaneously with epitope-bound bovine caseins as matrix proteins, and aldehyde-modified proteins were quantitated by a competition assay with a monoclonal antibody specific for acrolein-modified lysine or HNE-modified histidine epitopes. Minimal reaction times required for the coating/blocking; first monoclonal antibody and the peroxidase-conjugated second antibody binding steps were 3, 3, and 7 min, respectively, the former two steps being found to be or akin to diffusion-rate-limiting reactions. The convenient ELISA should find an application for analyses of the intricate processes involved in oxidative stress and carcinogenic insult. The epitope-attachment methodology may also be advantageous for the quantitation of various other biologically important haptenic molecules.

DOI： 10.1006/abio.1999.4073

Scopus

A 1-hour enzyme-linked immunosorbent assay for quantitation of acrolein- and hydroxynonenal-modified proteins by epitope-bound casein matrix method 査読有り国際誌

Satoh K, Yamada S, Koike Y, Igarashi Y, Toyokuni S, Kumano T, Takahata T, Hayakari M, Tsuchida S, Uchida K

ANALYTICAL BIOCHEMISTRY 270 巻 ( 2 ) 頁： 323 - 328 1999年6月

Intranuclear distribution of 8-hydroxy-2 '-deoxyguanosine: An immunocytochemical study

Toyokuni S, Iwasa Y, Kondo S, Tanaka T, Ochi H, Hiai H

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY 47 巻 ( 6 ) 頁： 833 - 835 1999年6月

Intranuclear distribution of 8-hydroxy-2'-deoxyguanosine: An immunocytochemical study

Toyokuni S., Iwasa Y., Kondo S., Tanaka T., Ochi H., Hiai H.

Journal of Histochemistry and Cytochemistry 47 巻 ( 6 ) 頁： 833 - 835 1999年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Histochemistry and Cytochemistry

We used immunofluorescence staining (monoclonal antibody N45.1) with cytological imprinting to study changes in the intranuclear distribution of 8-hydroxy-2'-deoxyguanosine in renal cells of male Wistar rats after oxidative stress by ferric nitrilotriacetate. In the control proximal tubule cells, small spherical signals were uniformly distributed throughout the nuclei. Under oxidative stress, immunofluorescence intensity was increased, especially near nuclear membrane. In cells with nuclear shrinkage or deformity, intense, diffuse signals throughout the nuclei were observed. Our results suggest that specific nuclear sites are vulnerable to oxidative DNA damage and that diffuse intense signals precede cell death after oxidative stress.

DOI： 10.1177/002215549904700613

Scopus

Intranuclear distribution of 8-hydroxy-2 '-deoxyguanosine: An immunocytochemical study

Toyokuni S, Iwasa Y, Kondo S, Tanaka T, Ochi H, Hiai H

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY 47 巻 ( 6 ) 頁： 833 - 835 1999年6月

Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes 査読有り国際誌

Ihara Y, Toyokuni S, Uchida K, Odaka H, Tanaka T, Ikeda H, Hiai H, Seino Y, Yamada Y

DIABETES 48 巻 ( 4 ) 頁： 927 - 932 1999年4月

Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes 査読有り国際誌

Ihara Y, Toyokuni S, Uchida K, Odaka H, Tanaka T, Ikeda H, Hiai H, Seino Y, Yamada Y

DIABETES 48 巻 ( 4 ) 頁： 927 - 932 1999年4月

Reactive oxygen species-induced molecular damage and its application in pathology

Toyokuni S.

Pathology International 49 巻 ( 2 ) 頁： 91 - 102 1999年3月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

Recent studies have clarified that reactive oxygen species (ROS) are involved in a diversity of biological phenomena including radiation damage, carcinogenesis, ischemia-reperfusion injury, diabetes mellitus and neurodegenerative diseases. The breakthrough of these fruitful accomplishments was the discovery of an enzyme, superoxide dismutase, by McCord and Fridovich in 1968. In the 1970s and 80s, biochemists and radiation biologists were attracted by the role of ROS in its irreversible damage to biological molecules. In the 1990s, ROS were further found to be a reversible modulator of protein structure as well, and this led to a recent rapid data accumulation on the association of ROS and transcription factors. At the same time, methods to localize ROS-induced damage in paraffin-embedded tissues have been established. This owes to a successful production of antibodies against covalently modified structures specific for ROS-induced damage. The epitopes include 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins. The present article reviews histochemical and immunohistochemical methods to localize ROS-induced damage in tissues and cells, further comments on the association of ROS with transcription factors, and shows a prospective view of ROS-induced carcinogenesis.

DOI： 10.1046/j.1440-1827.1999.00829.x

Scopus

Formation of 4-hydroxy-2-nonenal-modified proteins and 3-nitro-L-tyrosine in rat island skin flaps during and after ischemia 査読有り国際誌

Um SC, Suzuki S, Toyokuni S, Uchida K, Hiai H, Nishimura Y

ANNALS OF PLASTIC SURGERY 42 巻 ( 3 ) 頁： 293 - 298 1999年3月

Protection of ischemia-reperfusion lung against oxidative stress by nitroglycerin.

Kawashima, M; Bando, T; Nakamura, T; Yoshimura, T; Hanaoka, N; Hirata, T; Fukuse, T; Hasegawa, S; Toyokuni, S; Hitomi, S; Wada, H

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 159 巻 ( 3 ) 頁： A543 - A543 1999年3月

Protection of ischemia-reperfusion lung against oxidative stress by nitroglycerin. 国際誌

Kawashima, M, Bando, T, Nakamura, T, Yoshimura, T, Hanaoka, N, Hirata, T, Fukuse, T, Hasegawa, S, Toyokuni, S, Hitomi, S, Wada, H

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 159 巻 ( 3 ) 頁： A543 - A543 1999年3月

Formation of 4-hydroxy-2-nonenal-modified proteins and 3-nitro-L- tyrosine in rat island skin flaps during and after ischemia 査読有り国際誌

Um S.C., Suzuki S., Toyokuni S., Uchida K., Hiai H., Nishimura Y.

Annals of Plastic Surgery 42 巻 ( 3 ) 頁： 293 - 298 1999年3月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Annals of Plastic Surgery

4-Hydroxy-2-nonenal (HNE)-modified proteins and 3-nitro-L-tyrosine were evaluated as a specific marker of reactive oxygen species (ROS)- and nitric oxide (NO)-mediated peroxynitrite-induced tissue injuries in ischemic and reperfused skin flap by Western blot analysis. Specimens were taken from island skin flaps of rats during the following three conditions: ischemia only, 5 hours of ischemia and reperfusion, and 10 hours of ischemia and reperfusion. HNE-modified proteins and 3-nitro-L-tyrosine increased with ischemic time (3, 6, and 10 hours postischemia). In the reperfused skin flap after both 5 and 10 hours of ischemia, HNE-modified proteins and 3-nitro-L- tyrosine were increased 3 hours postreperfusion, and they reached a maximum 6 hours after reperfusion. HNE-modified proteins and 3-nitro-L-tyrosine 1 hour postreperfusion were higher with 10 hours ischemia-reperfusion than with 5 hours ischemia-reperfusion. These results indicate (1) that ROS- and NO- induced peroxynitrite-mediated cytotoxicity in ischemic flaps is dependent on the ischemic period and (2) that ROS- and NO-induced peroxynitrite-mediated cytotoxicity occurs during an early stage of reperfusion if the ischemic period is long.

DOI： 10.1097/00000637-199903000-00011

Scopus

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Reactive oxygen species-induced molecular damage and its application in pathology

Toyokuni Shinya

Pathology international 49 巻 ( 2 ) 頁： 91 - 102 1999年2月

Reactive oxygen species-induced molecular damage and its application in pathology

Toyokuni S

PATHOLOGY INTERNATIONAL 49 巻 ( 2 ) 頁： 91 - 102 1999年2月

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