Differential chromosome sensitivity to 5-azacytidine in Alzheimer's disease.
BACKGROUND
The methylation process in the DNA has been considered a control mechanism of gene activity, connected with genetic imprinting. 5-Azacytidine (5-AZC) is known to be a demethylation agent.


OBJECTIVE
We studied the cytogenetic effect of 5-AZC in Alzheimer's disease patients and in two control groups.


METHODS
Peripheral lymphocyte cultures derived from 8 patients with Alzheimer's disease and 8 elderly and 8 healthy young individuals, all female, were studied. The parameters investigated were: the undercondensation of constitutive heterochromatin of chromosomes 1, 9, and 16: the number of lesions in fragile sites 1q42 and 19q13; heterochromatin association, and the total number of induced lesions.


RESULTS
Our results showed a significantly increased frequency of undercondensation of chromosomes 1, 9, and 16 in Alzheimer's disease patients when compared with elderly and young healthy groups.


CONCLUSIONS
These results suggest that the demethylating action of 5-AZC could reveal differential gene activity in the Alzheimer group at the level of cellular division.
Departamento de Morfologia, Disciplina de Genética, UNIFESP/Escola Paulista de Medicina, São Paulo, Brazil.spepavao.morf@epm.br
S L
SL
Payão
M D
MD
Smith
P H
PH
Bertolucci
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology*; D002878:Chromosomes, Human, Pair 1 / Q000187:drug effects*; D002885:Chromosomes, Human, Pair 16 / Q000187:drug effects*; D002899:Chromosomes, Human, Pair 9 / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D006570:Heterochromatin / Q000187:drug effects; D006801:Humans; D008297:Male; D008745:Methylation / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D006570:Heterochromatin; D004247:DNA; D001374:Azacitidine