Repair of O6-methylguanine in rat pancreatic beta-cells after exposure to N-methyl-N-nitrosourea.
Diabetes
; 42(8): 1187-94, 1993 Aug.
Article
em En
| MEDLINE
| ID: mdl-8325451
ABSTRACT
Because of the possible involvement of O6-methyldeoxyguanosine as a cytotoxic and carcinogenic lesion in pancreatic beta-cells, studies were undertaken to assess the ability of rat beta-cells to repair this DNA lesion. Primary cultures of neonatal rat beta-cells were shown to contain very low levels of O6-methylguanine-DNA-methyltransferase activity, the predominant mechanism for repairing O6-methyldeoxyguanosine in mammalian cells. However, using a 32P-endlabeling assay to measure O6-methyldeoxyguanosine in cells after exposure to N-methyl-N-nitrosourea, it was determined that rat beta-cells repaired O6-methyldeoxyguanosine to a substantial extent over a 24-h period. To elucidate the mechanism of O6-methyldeoxyguanosine repair in the virtual absence of constitutive O6-methylguanine-DNA-methyltransferase expression, studies were performed to determine if O6-methylguanine-DNA-methyltransferase expression was enhanced in N-methyl-N-nitrosourea-treated beta-cells. No increase in O6-methylguanine-DNA-methyltransferase activity was detected 24 or 48 h after exposure. However, Northern blot analysis showed a two- to threefold elevation in O6-methylguanine-DNA-methyltransferase messenger RNA levels in beta-cells 12 and 24 h after N-methyl-N-nitrosourea treatment. This finding is the first demonstration of a change in O6-methylguanine-DNA-methyltransferase messenger RNA levels in a cell type with low constitutive activity.
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Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Guanina
/
Metilnitrosoureia
/
Metiltransferases
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
1993
Tipo de documento:
Article