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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
50
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pubmed:dateCreated |
2003-12-8
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pubmed:abstractText |
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 acrolein-modified 2' -deoxyadenosine. On the basis of chemical and spectroscopic evidence, the major antigenic product of mAb21 was the 1,N6-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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,N(6)-propanodeoxyadenosine,
http://linkedlifedata.com/resource/pubmed/chemical/2'-deoxyadenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Acrolein,
http://linkedlifedata.com/resource/pubmed/chemical/Aldehydes,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyadenosines,
http://linkedlifedata.com/resource/pubmed/chemical/Ions,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
50346-54
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pubmed:meshHeading |
pubmed-meshheading:14522963-Acrolein,
pubmed-meshheading:14522963-Aldehydes,
pubmed-meshheading:14522963-Animals,
pubmed-meshheading:14522963-Antibodies, Monoclonal,
pubmed-meshheading:14522963-Binding, Competitive,
pubmed-meshheading:14522963-Cattle,
pubmed-meshheading:14522963-Cell Nucleus,
pubmed-meshheading:14522963-DNA Adducts,
pubmed-meshheading:14522963-Deoxyadenosines,
pubmed-meshheading:14522963-Dose-Response Relationship, Drug,
pubmed-meshheading:14522963-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:14522963-Immunohistochemistry,
pubmed-meshheading:14522963-Ions,
pubmed-meshheading:14522963-Iron,
pubmed-meshheading:14522963-Lipid Peroxidation,
pubmed-meshheading:14522963-Liver,
pubmed-meshheading:14522963-Lysine,
pubmed-meshheading:14522963-Male,
pubmed-meshheading:14522963-Mice,
pubmed-meshheading:14522963-Mice, Inbred C57BL,
pubmed-meshheading:14522963-Mice, Transgenic,
pubmed-meshheading:14522963-Models, Chemical,
pubmed-meshheading:14522963-Neoplasms,
pubmed-meshheading:14522963-Oxidative Stress,
pubmed-meshheading:14522963-Oxygen,
pubmed-meshheading:14522963-Peroxidase,
pubmed-meshheading:14522963-Rats,
pubmed-meshheading:14522963-Rats, Wistar,
pubmed-meshheading:14522963-Threonine,
pubmed-meshheading:14522963-Thymus Gland,
pubmed-meshheading:14522963-Time Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Formation of acrolein-derived 2'-deoxyadenosine adduct in an iron-induced carcinogenesis model.
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pubmed:affiliation |
Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
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pubmed:publicationType |
Journal Article
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