Linked Life Data

12415124

Source:http://linkedlifedata.com/resource/pubmed/id/12415124

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2003-1-23
pubmed:abstractText
Although many questions remain unanswered, the general principle of the sequence of events leading to cancer after exposure to genotoxic carcinogens has become increasingly clear. This helps to understand the parameters that influence the shape of the dose-effect curve for carcinogenesis, including metabolic activation and inactivation of carcinogens, DNA repair, cell cycle control, apoptosis, and control by the immune system. A linear dose-response relationship with no observable threshold seems to be a conservative but adequate description for the carcinogenic activity of many genotoxic carcinogens, such as aflatoxin B1, the tobacco-specific nitrosoketone NNK, and probably N,N-diethylnitrosamine. However, extrapolation models connecting the high-level risk to the zero intercept have clearly resulted in overestimations of risk. Vinyl acetate is an example that is discussed extensively in this review. At extremely high and toxic doses, vinyl acetate is carcinogenic in rats and mice and causes chromosomal aberrations. In tissues of contact, vinyl acetate is converted to acetic acid and acetaldehyde. Only when threshold levels are achieved do critical steps in the mechanism ultimately leading to cancer become active, namely pH reduction in exposed cells of more than 0.15 units leading to cytotoxicity, damage to DNA, and regenerative proliferation. Consistent with the known exposure to endogenous acetic acid and acetaldehyde, tissues sustain a certain level of exposure without adverse effects. Physiological modeling shows that the conditions necessary for carcinogenesis are in place only when threshold levels of vinyl acetate are exceeded. The example of vinyl acetate underlines the importance of toxicological research that unequivocally identifies genotoxic carcinogens acting through a threshold process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0362-1642
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
485-520
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Challenging dogma: thresholds for genotoxic carcinogens? The case of vinyl acetate.
pubmed:affiliation
Institute of Toxicology, University of Mainz, D-55131 Mainz, Germany. hengstle@mail.Uni-Mainz.de
pubmed:publicationType
Journal Article, Review