Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma.

Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Research Abstract Details 

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Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Abstract Text:

Guang-Xun Li,Yoko Hirabayashi,Byung-Il Yoon,Yasushi Kawasaki,Isao Tsuboi,Yukio Kodama,Yuji Kurokawa,Junji Yodoi,Jun Kanno,Tohru Inoue,

OBJECTIVE: Reactive oxygen species (ROS), generated following benzene exposure, are considered to trigger the development of hematopoietic neoplasms, although little supporting evidence has been found. In this study, we examined whether the experimental elimination of ROS generated following benzene exposure prevents the development of benzene-induced hematopoietic disorders to clarify the mechanism underlying the development of benzene-induced hematopoietic disorders. METHODS: C57BL/6 mice, overexpressing human thioredoxin (h-Trx-Tg), were used to examine the possible nullification of ROS induction following benzene exposure. The experimental group was exposed to 300 ppm benzene 6 hours/day, 5 days/week, for 26 weeks, and lifetime observation followed by molecular and histopathological examinations were carried out. RESULTS: The present study using h-Trx-Tg mice showed a complete suppression of the development of thymic lymphoma induced by benzene inhalation (0% in h-Trx-Tg vs 30% in wild-type (Wt) mice). This was associated with a 48% decrease in the incidence of clastogenic micronucleated reticulocyte induction in the h-Trx-Tg mice compared with the Wt control after 2 weeks of inhalation. As underlying mechanisms, the attenuation of oxidative stress was accompanied by a complete abrogation of hemato-lymphoid toxicity, as shown by the upregulation of the activity of superoxide-dismutase, and a consequently stable ROS level, as determined by cell sorting using 2', 7'-dichlorodihydrofluorescein diacetate, along with a significant attenuation of the overexpression of a cell cycle-dependent kinase inhibitor, p21. CONCLUSION: The attenuation of benzene-induced oxidative stress and that of the consequent lymphomagenesis were observed for the first time, and these indicate a role of oxidative stress in benzene-induced clastogenesis and lymphomagenesis. (These attenuations were not seen in nonthymic lymphomas, and no leukemias developed in C57BL/6 used in this study.) During the constitutive overexpression of h-Trx, the expression of aryl-hydrocarbon receptor in h-Trx-Tg mice was downregulated, which may also contribute to the attenuation.

Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Publishing Authors By Initials

GX Li,Y Hirabayashi,BI Yoon,Y Kawasaki,I Tsuboi,Y Kodama,Y Kurokawa,J Yodoi,J Kanno,T Inoue,

For similar tissues: lymphoid tissue: thymus gland research abstracts see: tissues: lymphoid tissue: thymus gland research

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Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental hematology

VOLUME: 34

Page Numbers: 1687-97

Journal Abbreviation: Exp. Hematol.

ISSN: 0301-472X

DAY: 27

MONTH: Dec

YEAR: 2006

Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Information

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LANGUAGE: eng

NlmUniqueID: 402313

Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Keywords Mesh Terms:

KEYWORDS: Thymus Gland

MESH TERMS: pathology

Chemical & Substance for Abstract: Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Information

Substance Name: Cytochrome P-450 CYP2E1

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma.

AFFILIATION: Division of Cellular and Molecular Toxicology, Biological Safety and Research Center, National Institute of Health Sciences, Tokyo, Japan.

Country: Netherlands

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MEDLINETA: Exp Hematol

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