Killing and mutation of human lymphoblast cells by aflatoxin B1: evidence for an inducible repair response.
Cancer Res
; 47(8): 1993-2001, 1987 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-3103909
ABSTRACT
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos
/
Aflatoxinas
/
Reparación del ADN
/
Mutación
Límite:
Humans
Idioma:
En
Revista:
Cancer Res
Año:
1987
Tipo del documento:
Article