The chloroethylnitrosoureas: sensitivity and resistance to cancer chemotherapy at the molecular level.
Cancer Invest
; 15(6): 588-98, 1997.
Article
em En
| MEDLINE
| ID: mdl-9412665
ABSTRACT
The chloroethylnitrosoureas were developed in a synthetic program that began with the observation that N-methyl-N'-nitro-N-nitrosoguanidine was an effective agent against L1210 cells. The antitumor activity of the chloroethylnitrosoureas is based on their reactions with DNA, especially the formation of a cytosine-guanine crosslink in DNA. Resistance occurs when the enzyme, O6-alkylguanine-DNA alkyltransferase, repairs an intermediate in crosslink formation. Inhibition of O6-alkylguanine-DNA alkyltransferase often restores sensitivity to the chloroethlylnitrosoureas although evidence is accumulating that other repair mechanisms may also contribute to the resistance phenomenon. Continuing investigations in this field center on finding agents whose reactions with DNA are more specific, on elucidating other resistance mechanisms, and on overcoming resistance by developing new inhibitors of repair enzymes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistencia a Medicamentos Antineoplásicos
/
Reparo do DNA
/
Antineoplásicos
/
Compostos de Nitrosoureia
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Invest
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM