Linked Life Data

16122766

Source:http://linkedlifedata.com/resource/pubmed/id/16122766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2006-1-23
pubmed:abstractText
Aflatoxin B1 (AFB(1)) is a potent human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In human, AFB(1) is bioactivated by cytochrome P450 (CYP450) enzymes, primarily CYP1A2, to the genotoxic epoxide that forms N(7)-guanine DNA adducts. To characterize the transcriptional responses to genotoxic insults from AFB(1), a strain of Saccharomyces cerevisiae engineered to express human CYP1A2 was exposed to doses of AFB(1) that resulted in minimal lethality, but substantial genotoxicity. Flow cytometric analysis demonstrated a dose and time dependent S phase delay under the same treatment conditions, indicating a checkpoint response to DNA damage. Replicate cDNA microarray analyses of AFB(1) treated cells showed that about 200 genes were significantly affected by the exposure. The genes activated by AFB(1)-treatment included RAD51, DUN1 and other members of the DNA damage response signature reported in a previous study with methylmethane sulfonate and ionizing radiation [A.P. Gasch, M. Huang, S. Metzner, D. Botstein, S.J. Elledge, P.O. Brown, Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p, Mol. Biol. Cell 12 (2001) 2987-3003]. However, unlike previous studies using highly cytotoxic doses, environmental stress response genes [A.P. Gasch, P.T. Spellman, C.M. Kao, O. Carmel-Harel, M.B. Eisen, G. Storz, D. Botstein, P.O. Brown, Genomic expression programs in the response of yeast cells to environmental changes, Mol. Biol. Cell 11 (2000) 4241-4257] were largely unaffected by our dosing regimen. About half of the transcripts affected are also known to be cell cycle regulated. The most strongly repressed transcripts were those encoding the histone genes and a group of genes that are cell cycle regulated and peak in M phase and early G1. These include most of the known daughter-specific genes. The rapid and coordinated repression of histones and M/G1-specific transcripts cannot be explained by cell cycle arrest, and suggested that there are additional signaling pathways that directly repress these genes in cells under genotoxic stress.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
593
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
121-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Analysis of cellular responses to aflatoxin B(1) in yeast expressing human cytochrome P450 1A2 using cDNA microarrays.
pubmed:affiliation
Departmental of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural