Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Induction of oxidative single- and double-strand breaks in DNA by ferric citrate

Toyokuni S., Sagripanti J.

Free Radical Biology and Medicine Vol. 15 ( 2 ) page： 117 - 123 1993.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Free Radical Biology and Medicine

The relative risk of primary hepatocellular carcinoma in genetic hemochromatosis (GH) is estimated at over 200 times as that of control populations. Recently, ferric ion chelated to citrate (Fe-citrate) was identified as the major non-transferrin-bound iron in the serum of GH patients. We investigated whether low concentration of Fe-citrate plus reductant could damage supercoiled plasmid DNA under physiological pH and ionic strength. Incubation of Fe-citrate with either H2O2, l-ascorbate, or l-cysteine induced single- and double-strand breaksin supercoiled plasmid pZ189 in a concentration- and time-dependent fashion. DNA strand breaks produced by Fe-citrate plus H2O2 increased at reduced pH (≤ 6.9). Catalase and free radical scavengers inhibited the DNA breakage produced by Fe-citrate in combination with each reductant, suggesting that H2O2 and finally .OH are responsible DNA damaging species. The catalytic ability of Fe-citrate to induce DNA strand breaks, particularly double-strand breaks (DSBs), may contribute to the carcinogenic processes observed in GH. © 1993.

DOI： 10.1016/0891-5849(93)90050-5

Scopus

GENETIC PREDISPOSITION TO PRE-B LYMPHOMAS IN SL/KH STRAIN MICE International journal

YAMADA, Y, SHIMADA, M, OKAMOTO, K, TOYOKUNI, S, NAKAKUKI, Y, FUKUMOTO, M, HIAI, H

EXPERIMENTAL HEMATOLOGY Vol. 21 ( 8 ) page： 1118 - 1118 1993.8

ABNORMAL BONE-MARROW B-CELL DIFFERENTIATION IN PRE-B LYMPHOMA-PRONE SL/KH MICE Reviewed International journal

OKAMOTO, K, YAMADA, Y, SHIMADA, M, TOYOKUNI, S, NAKAKUKI, Y, HIAI, H

EXPERIMENTAL HEMATOLOGY Vol. 21 ( 8 ) page： 1126 - 1126 1993.8

GLUTATHIONE CYCLE DEPENDENCY OF FERRIC NITRILOTRIACETATE-INDUCED LIPID-PEROXIDATION IN MOUSE PROXIMAL RENAL TUBULES

OKADA S, MINAMIYAMA Y, HAMAZAKI S, TOYOKUNI S, SOTOMATSU A

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 301 ( 1 ) page： 138 - 142 1993.2

GLUTATHIONE CYCLE DEPENDENCY OF FERRIC NITRILOTRIACETATE-INDUCED LIPID-PEROXIDATION IN MOUSE PROXIMAL RENAL TUBULES

OKADA S, MINAMIYAMA Y, HAMAZAKI S, TOYOKUNI S, SOTOMATSU A

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 301 ( 1 ) page： 138 - 142 1993.2

Glutathione cycle dependency of ferric nitrilotriacetate-induced lipid peroxidation in mouse proximal renal tubules

Okada S., Minamiyama Y., Hamazaki S., Toyokuni S., Sotomatsu A.

Archives of Biochemistry and Biophysics Vol. 301 ( 1 ) page： 138 - 142 1993.2

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Archives of Biochemistry and Biophysics

Parenteral administration of ferric nitrilotriacetate (Fe-NTA), a known carcinogen in mouse and rat kidneys, enhances iron-dependent lipid peroxidation (LP) and causes acute renal tubular necrosis. We assume that filtered Fe-NTA in vivo is rapidly reduced by cysteine, a component of glutathione which is hydrolyzed by γ-GTP and dipeptidase, and that this reduced iron initiates lipid peroxidation in the lumen. In addition, the fatty acid composition of phospholipids between the cortex and the medulla may differ, because only the proximal tubules (which are located mainly in the cortex) are known to be vulnerable to LP. We tested these assumptions in the present study. Gas chromatographic determination of fatty acid composition in five male and five female 6-week-old normal ddY mice showed the ratio of polyunsaturated fatty acids to saturated fatty acids plus C18:1, a single double-bond fatty acid, to be 0.98 ± 0.08 (av ± SD) in the male cortex and 1.00 ± 0.08 in the female cortex. In the male and female medulla, however, it was 0.78 ± 0.09 (P < 0.05, vs cortex) and 0.68 ± 0.04 (P < 0.01, vs cortex), respectively. Pretreatment of the animals with buthionine sulfoximine, a glutathione synthetase inhibitor, and a procedure that reduces total glutathione content in the kidneys, suppressed LP. Reduced thiobarbituric acid reactive substances were also observed in animals treated with AT-125, a γ-GTP inhibitor, and in animals with immature γ-GTP activity. These results are consistent with our assumptions. © 1993 Academic Press, Inc.

DOI： 10.1006/abbi.1993.1125

Scopus

DNA SINGLE-STRAND AND DOUBLE-STRAND BREAKS PRODUCED BY FERRIC NITRILOTRIACETATE IN RELATION TO RENAL TUBULAR CARCINOGENESIS

TOYOKUNI S, SAGRIPANTI JL

CARCINOGENESIS Vol. 14 ( 2 ) page： 223 - 227 1993.2

DNA single- and double-strand breaks produced by ferric nitrilotriacetate in relation to renal tubular carcinogenesis

TOYOKUNI S.

Carcinogenesis Vol. 14 ( 2 ) page： 223 - 227 1993.2

DNA single- and double-strand breaks produced by ferric nitrilotriacetate in relation to renal tubular carcinogenesis

Toyokuni S., Sagripanti J.

Carcinogenesis Vol. 14 ( 2 ) page： 223 - 227 1993.2

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Carcinogenesis

Fe(III) bound to a chelator, nitrilotriacetate (NTA), has been reported to induce a high frequency of adenocarcinoma localized to the proximal tubules of the kidney in rodents. In order to examine possible mechanisms for the carcinogenic activity, we investigated the in vitro production of single- and double-strand breaks in DNA mediated by iron alone or Fe-NTA chelate using supercoiled plasmid pZ189. Neither Fe(III) nor NTA alone broke DNA. Fe(III) plus NTA together mediated the efficient oxidative production of DNA single-and double-strand breaks in the presence of reducing agents (ascorbate » H2O2 > cysteine). The Fe(III): NTA ratio (1:4) that was found to be optimal for DNA strand breakage was similar to the ratio that produced adenocarcinomas in rodents. Maximal Fe-NTA-mediated DNA damage in vitro was induced under conditions of neutral pH, low ionic strength, presence of reducing agent and absence of albumin. These conditions are present exclusively in the cortical proximal tubules of the kidney, the only location where toxicity and carcinogenicity of Fe-NTA has been observed. Thus, localized DNA damage may explain the anatomic site preferred by Fe-NTA-induced carcinogenesis. © 1993 Oxford University Press.

DOI： 10.1093/carcin/14.2.223

Scopus

CHARACTERIZATION OF IMMORTALIZED CELL-LINES ISOLATED FROM A SOFT-TISSUE TUMOR-DERIVED FROM A RABBIT SUBCHRONICALLY EXPOSED TO 60HZ MAGNETIC-FIELDS AT 1-G

NING, JT; BUSHAR, G; LI, L; TOYOKUNI, S; THOMAS, D; CRESS, L; CZERSKA, EM; SWICORD, ML; ELSON, E; DAVIS, CC

ELECTRICITY AND MAGNETISM IN BIOLOGY AND MEDICINE page： 405 - 408 1993

DOSE-DEPENDENT HEALTH-EFFECTS EXHIBITED IN RABBITS EXPOSED TO 60HZ MAGNETIC-FIELDS AT 1 G AND 5 G

NING, JT; CZERSKA, EM; CASAMENTO, J; TOYOKUNI, S; SWICORD, ML; STCHARLES, C; EINSMANN, FE; PERRY, B; ELSON, E; DAVIS, CC

ELECTRICITY AND MAGNETISM IN BIOLOGY AND MEDICINE page： 845 - 848 1993

PATHOLOGICAL EVALUATION OF RABBITS SUBCHRONICALLY EXPOSED TO 60HZ MAGNETIC-FIELDS AT 1 G AND 5 G

NING, JT; TOYOKUNI, S; THOMAS, D; CZERSKA, EM; CASAMENTO, J; SWICORD, ML; DAVIS, CC; ELSON, E

ELECTRICITY AND MAGNETISM IN BIOLOGY AND MEDICINE page： 835 - 838 1993

PATHOLOGICAL EVALUATION OF RABBITS SUBCHRONICALLY EXPOSED TO 60HZ MAGNETIC-FIELDS AT 1 G AND 5 G International journal

NING, JT, TOYOKUNI, S, THOMAS, D, CZERSKA, EM, CASAMENTO, J, SWICORD, ML, DAVIS, CC, ELSON, E

ELECTRICITY AND MAGNETISM IN BIOLOGY AND MEDICINE page： 835 - 838 1993

DOSE-DEPENDENT HEALTH-EFFECTS EXHIBITED IN RABBITS EXPOSED TO 60HZ MAGNETIC-FIELDS AT 1 G AND 5 G International journal

NING, JT, CZERSKA, EM, CASAMENTO, J, TOYOKUNI, S, SWICORD, ML, STCHARLES, C, EINSMANN, FE, PERRY, B, ELSON, E, DAVIS, CC

ELECTRICITY AND MAGNETISM IN BIOLOGY AND MEDICINE page： 845 - 848 1993

CHARACTERIZATION OF IMMORTALIZED CELL-LINES ISOLATED FROM A SOFT-TISSUE TUMOR-DERIVED FROM A RABBIT SUBCHRONICALLY EXPOSED TO 60HZ MAGNETIC-FIELDS AT 1-G Reviewed International coauthorship International journal

NING, JT, BUSHAR, G, LI, L, TOYOKUNI, S, THOMAS, D, CRESS, L, CZERSKA, EM, SWICORD, ML, ELSON, E, DAVIS, CC

ELECTRICITY AND MAGNETISM IN BIOLOGY AND MEDICINE page： 405 - 408 1993

IRON-MEDIATED DNA DAMAGE - SENSITIVE DETECTION OF DNA STRAND BREAKAGE CATALYZED BY IRON

TOYOKUNI S, SAGRIPANTI JL

JOURNAL OF INORGANIC BIOCHEMISTRY Vol. 47 ( 3-4 ) page： 241 - 248 1992.8

REPORT OF A PATIENT WITH POEMS-TAKATSUKI-CROW-FUKASE SYNDROME ASSOCIATED WITH FOCAL SPINAL PACHYMENINGEAL AMYLOIDOSIS

TOYOKUNI S, EBINA Y, OKADA S, YAMABE H, ISHIKAWA T, UCHIYAMA T, YODOI J, UCHINO H, TAKATSUKI K

CANCER Vol. 70 ( 4 ) page： 882 - 886 1992.8

Report of a patient with POEMS/takatsuki/crow‐fukase syndrome associated with focal spinal pachymeningeal amyloidosis

Toyokuni S., Ebina Y., Okada S., Yamabe H., Ishikawa T., Uchiyama T., Yodoi J., Uchino H., Takatsuki K.

Cancer Vol. 70 ( 4 ) page： 882 - 886 1992.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer

The authors present the results of an autopsy of a 67‐year‐old Japanese man with POEMS/Takatsuki/Crow‐Fukase syndrome (P/T/CFS) diagnosed in 1972. Each component of the syndrome was gradually recognized after the resection of lumbar vertebral solitary plasma‐cytoma in 1967. The patient died in 1989 of generalized infection and renal failure. Autopsy revealed in the vertebral canal between the fifth and seventh thoracic vertebrae dorsal pachymeningeal fibrosis, with prominent amyloid deposition that oppressed the spinal cord. This condition was consistent with the final neurologic manifestation of the patient, bilateral motor and sensory disturbance below the sixth thoracic level. Myelopathy remained clinically unnoticed because neurologic disturbance had begun as peripheral polyneuropathy. Normo‐cellular marrow with heterogeneously scattered lambda light chain‐positive plasma cells and degeneration of the myelinated fibers of sciatic nerve also were observed. This is the first report of focal spinal amyloidosis associated with P/T/CFS. Cancer 1992; 70:882–886. Copyright © 1992 American Cancer Society

DOI： 10.1002/1097-0142(19920815)70:4<882::AID-CNCR2820700426>3.0.CO;2-R

Scopus

Peport of a patient with POEMS/Takatsuki/Crow-Fukase syndrome associated with focal spinal pachymeningeal amyloidsis.

TOYOKUNI S.

Cancer Vol. 70 ( 4 ) page： 882 - 886 1992.8

Iron-mediated DNA damage : sensitive detection of DNA strand breakage catalyzed by iron

TOYOKUNI S

J. Inorg. Biochem. Vol. 47 ( 3-4 ) page： 241 - 248 1992.8

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