The alkylating drug resistance is frequently related to the DNA repair activity O-6-alkylguanine-DNA alkyltransferase (O-6-AT), a protein coded by the methylguanine-DNA methyltransferase gene (MGMT). We synthesized one antisense oligodeoxyribonucleotide (AS-ODN) targeted against the mRNA of the MGMT gene. The administration of this ''antimessenger'' sequence to a Chinese hamster ovary cell line, expressing the transfected human MGMT gene, caused a moderate decrease of the resistance to the chloroethylating drug mitozolomide (MTZ), measured as induction of sister chromatid exchanges (SCE). The AS-ODN administration combined with depletion and recovery of O-6-AT by O-6-methylguanine inhibitor treatment showed an enhancement of SCE induction. The results support the inhibition of the MGMT translation mechanism by AS-ODN and suggest that the pre-existing protein could compromise the reversion of the resistant phenotype if is still active during the administration of the ''antimessenger'' sequence.
|Autori:||L. CITTI; BOLDRINI L; G. RAINALDI.|
|Titolo:||The genotoxicity of the chlroethylating agent Mitozolomide is enhanced in CHO MEX+ cells by the administration of antimessenger oligonucleotide targeted against Methylguanine-DNA methyltransferase gene (MGMT)|
|Anno del prodotto:||1994|
|Appare nelle tipologie:||1.1 Articolo in rivista|