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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1992-12-22
pubmed:abstractText
Chromium(VI) compounds exert their genotoxicity and mutagenicity by complex metabolic reducing pathways that generate a variety of reactive forms of chromium and free radicals. To investigate the molecular nature of chromium-induced mutations, we characterized the entire coding region of the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene of 27 independent mutants derived from chromium(VI) oxide (CrO3)-treated Chinese hamster ovary-K1 cells, by direct sequencing of PCR-amplified cDNA. Among these mutants, 10 consisted of single base substitutions, five contained two base substitutions, one had four base substitutions, six were splicing mutations, and five exhibited single base pair insertions or deletions. All of the base substitutions and most of the frameshift mutations observed were located at A/T-rich sequences. More than 90% of the base substitutions (22/24) occurred in A.T base pairs. Among them, T-->A and T-->G transversions (18/22) predominated. The mutational hotspots for single and double base substitutions were the 3' thymidine of 5'PuT and thymidines of 5'ATTT sequences respectively. This mutational specificity was also observed in CHO-K1 cells treated with two other chromium(VI) compounds, namely K2Cr2O7 and PbCrO4. Strand bias was noticed in chromium mutagenicity, since 77% of T base substitutions occurred on the non-transcribed strand. This highly sequence-specific mutation spectrum suggests that a particular form of chromium may directly interact with DNA at these hotspot sequences.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:geneSymbol
hprt
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2053-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Mutational specificity of chromium(VI) compounds in the hprt locus of Chinese hamster ovary-K1 cells.
pubmed:affiliation
Molecular and Genetic Toxicology Group, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't