Sex hormone-dependence of ferric nitrilotriacetate-induced lipid peroxidation in ddY mice

Toyokuni, Shinya; Okada, Shigeru; Hamazaki, Shuji; Minamiyama, Yukiko; Yamada, Yoshihiro; Liang, Ping

doi:10.1016/0891-5849(90)90795-k

Cited by 36 publications

(51 citation statements)

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“…The hematoxylin and eosin-stained sections of the paraffinembedded tissues were analyzed for histological damage. The morphological changes in the kidneys of rats treated with Fe 3ϩ -NTA versus time are very similar to previous reports on ddY mice (15,22). As shown in Fig.…”

Section: Formation Of Acrolein-2ј-deoxyadenosine Adduct In the Renal supporting

confidence: 89%

Formation of Acrolein-derived 2′-Deoxyadenosine Adduct in an Iron-induced Carcinogenesis Model

Kawai

Furuhata

Toyokuni

et al. 2003

Journal of Biological Chemistry

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Acrolein is a representative carcinogenic aldehyde found ubiquitously in the environment and formed endogenously through oxidation reactions, such as lipid peroxidation and myeloperoxidase-catalyzed amino acid oxidation. It shows facile reactivity toward DNA to form an exocyclic DNA adduct. To verify the formation of acrolein-derived DNA adduct under oxidative stress in vivo, we raised a novel monoclonal antibody (mAb21) against the acrolein-modified DNA and found that the antibody most significantly recognized an acroleinmodified 2 -deoxyadenosine. On the basis of chemical and spectroscopic evidence, the major antigenic product of mAb21 was the 1,N 6 -propano-2 -deoxyadenosine adduct. The exposure of rat liver epithelial RL34 cells to acrolein resulted in a significant accumulation of the acrolein-2 -deoxyadenosine adduct in the nuclei. Formation of this adduct under oxidative stress in vivo was immunohistochemically examined in rats exposed to ferric nitrilotriacetate, a carcinogenic iron chelate that specifically induces oxidative stress in the kidneys of rodents. It was observed that the acrolein-2 -deoxyadenosine adduct was formed in the nuclei of the proximal tubular cells, the target cells of this carcinogenesis model. The same cells were stained with a monoclonal antibody 5F6 that recognizes an acrolein-lysine adduct, by which cytosolic accumulation of acrolein-modified proteins appeared. Similar results were also obtained from myeloperoxidase knockout mice exposed to the iron complex, suggesting that the myeloperoxidase-catalyzed oxidation system might not be essential for the generation of acrolein in this experimental animal carcinogenesis model. The data obtained in this study suggest that the formation of a carcinogenic aldehyde through lipid peroxidation may be causally involved in the pathophysiological effects associated with oxidative stress.Lipid peroxidation leads to the formation of a broad array of different products with diverse and powerful biological activities. Among them are a variety of different aldehydes (1). The primary products of lipid peroxidation, lipid hydroperoxides (2), can undergo carbon-carbon bond cleavage via alkoxyl radicals in the presence of transition metals, giving rise to the formation of short chain, unesterified aldehydes (2, 3) or a second class of aldehydes still esterified to the parent lipid. These reactive aldehydic intermediates readily form covalent adducts with cellular macromolecules, including DNA, leading to disruption of important cellular functions and mutations. The important agents that give rise to the modification of DNA may be represented by ␣,␤-unsaturated aldehydic intermediates, such as 2-alkenals and 4-hydroxy-2-alkenals (4, 5). 2-Alkenals represent a group of highly reactive aldehydes containing two electrophilic reaction centers. A partially positive carbon 1 or 3 in such molecules can attack nucleophiles, such as protein and DNA, which leads to the formation of cyclic adducts or cross-links. Among all of the ␣,␤-unsaturated aldehydes, acro...

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Section: Formation Of Acrolein-2ј-deoxyadenosine Adduct In the Renal supporting

confidence: 89%

Formation of Acrolein-derived 2′-Deoxyadenosine Adduct in an Iron-induced Carcinogenesis Model

Kawai

Furuhata

Toyokuni

et al. 2003

Journal of Biological Chemistry

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“…Protein determination was done by the method of Lowry et al (23), using bovine serum albumin as a standard. (10,11). Briefly, cytoplasmic degeneration with pyknosis was observed at 1 hr in a small fraction of renal proximal tubules.…”

Section: Methodsmentioning

confidence: 99%

“…injections of Fe-NTA were reported to induce acute and subacute renal proximal tubular necrosis and a subsequent high incidence (60-92%) of renal adenocarcinoma in male rats and mice (4)(5)(6). We have shown in this model that lipid peroxidation as seen biochemically by thiobarbituric acid-reactive substances TBARS) and histochemically by the cold Schiffs method (detection of aldehydes) has been closely associated with carcinogenesis (7)(8)(9)(10)(11)(12). Lipid peroxidation has been implicated in causing a wide range ofbiological effects (13) including heart diseases, aging, retinal degeneration, and cancer.…”

Section: By _uans Of Anmentioning

confidence: 99%

Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate.

Toyokuni

Uchida²,

Okamoto³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

324

194

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An iron chelate, ferric nitrilotriacetate (Fe-NTA), Induces prox l tubular necrosis, a consequence of lipid peroxidatlon, that iall leads to a high Incidence of renal adenocarcinoma in rodents. Lipid peroidation as monitored by formation of thiobarbituric acdd-reactive suaces and bee 4-hydroxy-2-noena (HNE) was observed in the kidney homogenates of rats treated with Fe-NTA. Based on the fact that HNE is capable of reating with cellular proteins, we attempted to detect the localization of HNE-mopie proteins in rat kidney tissues with an immustochemical procedure.

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“…An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular damage, a consequence of a Fenton-like reaction in vivo, that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rodents (Ebina et al, 1986;Li et al, 1987;Toyokuni et al, 1990). Fe-NTA-induced renal carcinogenesis in rats is a unique model characterized by (1) high incidence of pulmonary metastasis and peritoneal invasion, (2) the presence of molecules covalently modified by reactive oxygen species (ROS) (Toyokuni, 1999) in the target organ during carcinogenesis and (3) inhibition of not only acute renal damage (Hamazaki et al, 1988) but also tumor incidence (Zhang et al, 1997) by pretreatment with a lipid-soluble antioxidant, a-tocopherol.…”

Section: Introductionmentioning

confidence: 99%

Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis

et al. 2004

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Sex hormone-dependence of ferric nitrilotriacetate-induced lipid peroxidation in ddY mice

Cited by 36 publications

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Formation of Acrolein-derived 2′-Deoxyadenosine Adduct in an Iron-induced Carcinogenesis Model

Formation of Acrolein-derived 2′-Deoxyadenosine Adduct in an Iron-induced Carcinogenesis Model

Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate.

Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis

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