Document Detail


Killing and mutation of human lymphoblast cells by aflatoxin B1: evidence for an inducible repair response.
MedLine Citation:
PMID:  3103909     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diploid human lymphoblast cells exhibit apparent saturation of mutation induced by exposure to aflatoxin B1, despite a linear increase in the amount and proportion of the aflatoxin-DNA adducts formed. The saturation is neither a cell cycle phenomenon nor a result of a genetically heterozygous population. Examination of the biphasic nature of aflatoxin-DNA adduct loss in vivo shows initial, rapid removal of all adduct species, followed by a slow loss of the aflatoxin-N7-guanine adduct alone. We hypothesize that these data reveal two modes of adduct loss in these cells. The first is an inducible, error-free system that is short-lived, turning off as adduct levels fall below the induction threshold of some 1000 total adducts/cell. The second loss is slower and results from spontaneous depurination of remaining aflatoxin-N7-guanines. Our data are in agreement with the possibility that apurinic sites thus generated are responsible for the mutation observed. A major paradox arises from the fact that aflatoxin-related premutagenic depurinations are estimated to be only 10% of the number of spontaneous depurinations estimated by others to occur in human cells in a 1-h period.
Authors:
D A Kaden; K M Call; P M Leong; E A Komives; W G Thilly
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  47     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1987 Apr 
Date Detail:
Created Date:  1987-05-04     Completed Date:  1987-05-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1993-2001     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aflatoxin B1
Aflatoxins / metabolism,  toxicity*
Cell Cycle / drug effects
Cell Line
Cell Survival / drug effects
DNA / metabolism
DNA Repair / drug effects*
Humans
Lymphocytes / drug effects*
Mutation*
Time Factors
Grant Support
ID/Acronym/Agency:
5-P01-ES00597/ES/NIEHS NIH HHS; 5-T32-ES07020-07/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Aflatoxins; 1162-65-8/Aflatoxin B1; 9007-49-2/DNA

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


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