研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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Biomarker evidence of DNA oxidation in lung cancer patients: Association of urinary 8-hydroxy-2'-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment

Erhola M, Toyokuni S, Okada K, Tanaka T, Hiai H, Ochi H, Uchida K, Osawa T, Nieminen MM, Alho H, KellokumpuLehtinen P

FEBS LETTERS 409 巻 ( 2 ) 頁： 287 - 291 1997年6月

Biomarker evidence of DNA oxidation in lung cancer patients: Association of urinary 8-hydroxy-2'-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment 査読有り国際共著国際誌

Erhola M, Toyokuni S, Okada K, Tanaka T, Hiai H, Ochi H, Uchida K, Osawa T, Nieminen MM, Alho H, KellokumpuLehtinen P

FEBS LETTERS 409 巻 ( 2 ) 頁： 287 - 291 1997年6月

Protection by αG-Rutin, a Water-soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

SHIMOI Kayoko, SHEN Bingrong, TOYOKUNI Shinya, MOCHIZUKI Rika, FURUGORI Michiyo, KINAE Naohide

Japanese journal of cancer research : gann 88 巻 ( 5 ) 頁： 453 - 460 1997年5月

Protection by αG-Rutin, a Water-soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

SHIMOI Kayoko, SHEN Bingrong, TOYOKUNI Shinya, MOCHIZUKI Rika, FURUGORI Michiyo, KINAE Naohide

Japanese journal of cancer research : gann 88 巻 ( 5 ) 頁： 453 - 460 1997年5月

Protection by alpha G-rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate

Shimoi K, Shen BR, Toyokuni S, Mochizuki R, Furugori M, Kinae N

JAPANESE JOURNAL OF CANCER RESEARCH 88 巻 ( 5 ) 頁： 453 - 460 1997年5月

Protection by αG-Rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate

Shimoi K., Shen B., Toyokuni S., Mochizuki R., Furugori M., Kinae N.

Japanese Journal of Cancer Research 88 巻 ( 5 ) 頁： 453 - 460 1997年5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：Japanese Journal of Cancer Research

The protective effect of αG-Rutin against ferric nitrilotriacetate (Fe-NTA)-induced renal damage was studied in male ICR mice. Fe-NTA induces renal lipid peroxidation, leading to a high incidence of renal cell carcinoma in rodents. Administration of αG-Rutin (50 μmol as rutin/kg) by gastric intubation 30 min after i.p. injection of Fe-NTA (7 mg Fe/kg) most effectively suppressed renal lipid peroxidation. Repeated i.p. injection of Fe-NTA (2 mg Fe/kg/day for the first 3 days and 3 mg Fe/kg/day for 12 days, 5 days a week) causes subacute nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal tubules. A protective effect was observed in mice given αG-Rutin 30 min after each Fe-NTA treatment. To elucidate the mechanism of protection by αG-Rutin, the pharmacokinetics and hydroxyl radical-scavenging effect of αG-Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), respectively. When mice were given αG-Rutin (50 μmol as rutin/kg) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of αG-Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min. αG-Rutin inhibited the formation of DMPO-OH in a concentration-dependent manner. Further, chelating activity of αG-Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed αG-Rutin works as an antioxidant in vivo either by scavenging reactive oxygen species or by chelating ferric ions and this serves to prevent oxidative renal damage in mice treated with Fe-NTA.

DOI： 10.1111/j.1349-7006.1997.tb00403.x

Scopus

Protection by alpha G-rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate

Shimoi K, Shen BR, Toyokuni S, Mochizuki R, Furugori M, Kinae N

JAPANESE JOURNAL OF CANCER RESEARCH 88 巻 ( 5 ) 頁： 453 - 460 1997年5月

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats 査読有り国際誌

Ma YX, Zhang DX, Kawabata T, Kiriu T, Toyokuni S, Uchida K, Okada S

PATHOLOGY INTERNATIONAL 47 巻 ( 4 ) 頁： 203 - 208 1997年4月

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats

Ma Yuxiang, Zhang Daxian, Kawabata Teruyuki

Pathology international 47 巻 ( 4 ) 頁： 203 - 208 1997年4月

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats 査読有り

YX Ma, DX Zhang, T Kawabata, T Kiriu, S Toyokuni, K Uchida, S Okada

PATHOLOGY INTERNATIONAL 47 巻 ( 4 ) 頁： 203 - 208 1997年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BLACKWELL SCIENCE

The copper and iron status in the liver of non-tumor bearing Long-Evans Cinnamon (LEC) rats (average age 17 months) was investigated. A direct quantitation of loosely-bound copper anti iron was also investigated by using a chelating agent, nitrilotriacetic acid (NTA-chelatable free copper and iron). Besides the total copper and iron contents, the level of NTA-chelatable free copper was also higher in LEC rats than in LEA rats (P<0.05). But for the free iron level there was no significant difference between the two rat groups (P>0.05). The formation of thiobarbituric acid-reactive substances was higher in LEC rats than in LEA mts (P<0.01). The 4-hydroxy-2-nonenal (HNE)-modified proteins were also clearly demonstrated in LEC rat liver. The copper and iron which produced the most important effect in the process of oxidative damage in LEC rats could not be distinguished. Even though free copper, which could induce free radical injuries, was increased in LEC rats, neither tumor-induction nor preneoplastic lesions in the experimental LEC rats were observed. therefore it is speculated that the elevation of a free iron is another important factor. Copper and iron, both important transition metals In the body, may participate in the induction of DNA damage and oncogenesis.

DOI： 10.1111/j.1440-1827.1997.tb04481.x

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Quantitative immunohistochemical determination of 8-hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: Its application to ferric nitrilotriacetate-induced renal carcinogenesis model 査読有り国際誌

Toyokuni S, Tanaka T, Hatton Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T

LABORATORY INVESTIGATION 76 巻 ( 3 ) 頁： 365 - 374 1997年3月

Toyokuni S, Tanaka T, Hatton Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T

LABORATORY INVESTIGATION 76 巻 ( 3 ) 頁： 365 - 374 1997年3月

Quantitative immunohistochemical determination of 8-hydroxy-2'- deoxyguanosine by a monoclonal antibody N45.1: Its application to ferric nitrilotriacetate-induced renal carcinogenesis model 査読有り国際誌

Toyokuni S., Tanaka T., Hattori Y., Nishiyama Y., Yoshida A., Uchida K., Hiai H., Ochi H., Osawa T.

Laboratory Investigation 76 巻 ( 3 ) 頁： 365 - 374 1997年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Laboratory Investigation

The DNA base-modified product 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most commonly used markers for the evaluation of oxidative DNA damage. A monoclonal antibody specific for 8-OHdG (N45.1) was characterized end applied in quantitative immunohistochemistry. N45.1 recognized both the modified base and deoxyribose structure of 8-OHdG and required a concentration two orders higher of 8-hydroxyguanosine as a competitor in the ELISA. In addition, N45.1 did not cross-react with the original four deoxyribonucleosides, other DNA base-modified products such as 8-hydroxy-2'- deoxyadenosine and O6-methyl-2'-deoxyguanosine, or urine components such as uric acid, creatine, and creatinine. A ferric nitrilotriacetate-induced rat renal carcinogenesis model was used for the evaluation of quantitative immunohistochemistry. The 8-OHdG index of quantitative immunohistochemistry, as analyzed by NIH Image freeware, correlated reasonably well with the 8- OHdG amount determined by high-performance liquid chromatography with an electrochemical detector-except for a difference in peak time, which could be attributed to the selection of target location. The present method has advantages over the high-performance liquid chromatography/electrochemical detector, gas chromatography/mass spectrometry, and 32P-postlabeling methods in that it allows localization of 8-OHdG to be specified without the risk of artifactual production of 8-OHdG during the DNA extraction and hydrolytic processes.

Scopus

Quantitative immunohistochemical determination of 8-hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model.

Toyokuni S, Tanaka T, Hattori Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T

Laboratory investigation; a journal of technical methods and pathology 76 巻 ( 3 ) 頁： 365 - 74 1997年3月

Overexpression of Integrin-associated Protein (CD47) in Rat Kidney Treated with a Renal Carcinogen, Ferric Nitrilotriacetate

NISHIYAMA Yasuyuki, TANAKA Tomoyuki, NAITOH Hiroshi, MORI Chisato, FUKUMOTO Manabu, HIAI Hiroshi, TOYOKUNI Shinya

Japanese journal of cancer research : gann 88 巻 ( 2 ) 頁： 120 - 128 1997年2月

Overexpression of Integrin-associated Protein (CD47) in Rat Kidney Treated with a Renal Carcinogen, Ferric Nitrilotriacetate

NISHIYAMA Yasuyuki, TANAKA Tomoyuki, NAITOH Hiroshi, MORI Chisato, FUKUMOTO Manabu, HIAI Hiroshi, TOYOKUNI Shinya

Japanese journal of cancer research : gann 88 巻 ( 2 ) 頁： 120 - 128 1997年2月

Induction of a wide range of C<inf>2-12</inf> aldehydes and C<inf>7-12</inf> acyloins in the kidney of wistar rats after treatment with a renal carcinogen, ferric nitrilotriacetate

Toyokuni S., Luo X.P., Tanaka T., Uchida K., Hiai H., Lehotay D.C.

Free Radical Biology and Medicine 22 巻 ( 6 ) 頁： 1019 - 1027 1997年2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：Free Radical Biology and Medicine

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular necrosis associated with lipid peroxidation and oxidative DNA damage that finally leads to a high incidence of renal cell carcinoma in rodents. In the present study, we investigated what kinds of C2-12 saturated and unsaturated aldehydes and C7-12 acyloins, metabolites of saturated aldehydes, are produced in the kidney and liver within 24 h after single ip administration of 15 mg Fe/kg of Fe-NTA, or after repeated (1 or 3 wk) ip administration of 5-10 mg Fe/kg of Fe-NTA. Amounts of twenty one aldehydes and five acyloins were determined by capillary column gas chromatography-negative-ion chemical ionization mass spectrometry with ammonia as reagent gas. Most of the aldehydes and all the acyloins measured revealed a significant dose-dependent increase 1 to 3 h after single administration in the kidney, among which 4-hydroxy-2-nonenal (HNE) showed the highest increase (27.3-fold) and malondialdehyde (MDA) was the most abundant aldehyde (2.40 nmol/100 mg wet tissue). In the liver, however, the increase in aldehydes and acyloins was less prominent. After repeated administration of Fe-NTA, only 9 aldehydes (ethanal; furfural; trans, trans- 2,4-heptadienal; nonanal; trans-2, cis-6 nonadienal; HNE; decanal; trans-4, cis-4-decenal; MDA) and 4 acyloins (3-hydroxyheptan-2-one; 3-hydroxyoctan-2- one; 3-hydroxynonan-2-one; 3-hydroxydodecan-2-one) showed a significant increase. Immunohistochemistry further demonstrated an increased amount of HNE-modified and MDA-modified proteins in the renal proximal tubules after repeated Fe-NTA administration. Some of the aldehydes measured such as HNE and MDA are reportedly cytotoxic, genotoxic and mutagenic. Accumulation of these aldehydes may play a role in this renal carcinogenesis model.

DOI： 10.1016/S0891-5849(96)00489-3

Scopus

8-hydroxy-2'-deoxyguanosine is increased in epidermal cells of hairless mice after chronic ultraviolet B exposure (vol 107, pg 733, 1996)

Hattori, Y; Nishigori, C; Tanaka, T; Uchida, K; Nikaido, O; Osawa, T; Hiai, H; Imamura, S; Toyokuni, S

JOURNAL OF INVESTIGATIVE DERMATOLOGY 108 巻 ( 2 ) 頁： 237 - 237 1997年2月

Overexpression of integrin-associated protein (CD47) in rat kidney treated with a renal carcinogen, ferric nitrilotriacetate

Nishiyama Y, Tanaka T, Naitoh H, Mori C, Fukumoto M, Hiai H, Toyokuni S

JAPANESE JOURNAL OF CANCER RESEARCH 88 巻 ( 2 ) 頁： 120 - 128 1997年2月

Induction of a wide range of C-2-12 aldehydes and C-7-12 acyloins in the kidney of Wistar rats after treatment with a renal carcinogen, ferric nitrilotriacetate 査読有り国際誌

Toyokuni S, Luo XP, Tanaka T, Uchida K, Hiai H, Lehotay DC

FREE RADICAL BIOLOGY AND MEDICINE 22 巻 ( 6 ) 頁： 1019 - 1027 1997年

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