Linked Life Data

11909755

Source:http://linkedlifedata.com/resource/pubmed/id/11909755

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-3-22
pubmed:abstractText
Aristolochic acid (AA) is found in a plant that causes urothelial carcinomas in patients with Chinese herb nephropathy (CHN). To evaluate the in vivo mutagenicity of AA, we analysed the mutant frequency (MF) in the lacZ and cII gene of 10 organs of the lambda/lacZ transgenic mouse (MutaMouse) after intragastric treatment with AA (15mg/kg per week x 4). Simultaneously, the clastogenicity of AA was evaluated by the peripheral blood micronucleus assay. The nature of the mutations induced by AA was revealed by the sequence analysis of the cII gene, which is also a phenotypically selectable marker in the lambda transgene. MFs in the target organs-forestomach, kidney, and bladder of AA-treated mice were significantly higher than those of control mice (forestomach 33- and 15-fold; kidney 10- and 9-fold; bladder 16- and 31-fold, for the lacZ and cII, respectively). The MFs in non-target organs, except the colon, showed only slight increases. Sequence analysis of cII mutants in target organs revealed that AA induced mainly A:T to T:A transversions whereas G:C to A:T transitions at CpG sites predominated among spontaneous mutations. These results suggested that AA, which is activated by cytochrome P450 and peroxidase to form cyclic nitrenium ions that bind to deoxyadenine, caused the A to T transversions in the target organs of mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
515
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
63-72
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Mutagenicity of aristolochic acid in the lambda/lacZ transgenic mouse (MutaMouse).
pubmed:affiliation
Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan.
pubmed:publicationType
Journal Article