Document Detail


Correlation of DNA adduct levels with tumor incidence: carcinogenic potency of DNA adducts.
MedLine Citation:
PMID:  10064864     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The quantitative relationship between DNA adducts and tumor incidence is evaluated in this review. All available data on DNA adduct levels determined after repeated administration of a carcinogen to rats or mice have been compiled. The list comprised 27 chemicals, of all major structural classes of carcinogens. For the correlation with tumor incidence, the DNA adduct levels measured at the given dose were normalized to the dose which resulted in a 50% tumor incidence under the conditions of a 2-year bioassay (TD50 dose). In rat liver, the calculated adduct concentration 'responsible' for a 50% hepatocellular tumor incidence spanned from 53 to 2083 adducts per 108 nucleotides, for aflatoxin B1, tamoxifen, IQ, MeIQx, 2,4-diaminotoluene, and dimethylnitrosamine (in this order). In mouse liver, the respective figures were 812 to 5543 adducts per 108 nucleotides, for ethylene oxide, dimethylnitrosamine, 4-aminobiphenyl, and 2-acetylaminofluorene. The observed span (40-fold in rats, 7-fold in mice) reflects differences between the various DNA adducts to lead to critical mutations. If additional carcinogens fit in with this astonishingly narrow range, the measurement of DNA adduct levels in target tissue has the potential to be not only an exposure marker but an individual cancer risk marker. For toremifen and styrene, low levels of DNA adducts were detected in rat liver at the end of a negative long-term bioassay. This shows that the limit of detection of DNA adducts can be well below the limit of detection of an increased tumor incidence. For a cancer risk assessment at low levels of DNA damage, treatment-related adducts must be discussed in relation to the background DNA damage and its inter- and intraindividual variability.
Authors:
M Otteneder; W K Lutz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Mutation research     Volume:  424     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-05-05     Completed Date:  1999-05-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  237-47     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Elsevier Science B.V.
Affiliation:
Department of Toxicology, University of Wuerzburg, Versbacher Strasse 9, D-97078, Wuerzburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinogens / adverse effects
DNA Adducts* / drug effects
DNA, Neoplasm / genetics
Humans
Mice
Neoplasms / genetics*
Neoplasms, Experimental / genetics*
Rats
Risk Factors
Chemical
Reg. No./Substance:
0/Carcinogens; 0/DNA Adducts; 0/DNA, Neoplasm

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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