Mutagenic activity and DNA adduct formation by 1, 2-epoxy-3-(p-nitrophenoxy)propane, an HIV-1 protease inhibitor and GST substrate.
Biochem Biophys Res Commun
; 261(3): 844-7, 1999 Aug 11.
Article
em En
| MEDLINE
| ID: mdl-10441513
ABSTRACT
Acid protease inhibitor 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) is commonly used in research as a substrate for glutathione-S-transferase activity (GST) and recently was found to inhibit human immunodeficiency virus 1 (HIV-1) protease. The question of DNA-adduct formation and mutagenicity was investigated and found that ENPP causes DNA damage and acts directly to induce mutagenicity in Salmonella. Using HPLC analysis, ENPP was shown to bind covalently to guanine residues. The Salmonella mutagenicity assay indicated that ENPP enhanced the mutation frequencies in the base-substitution strain TA00 by more than 20 times above the background. Its mutagenic potency was comparable to that of well-known carcinogens, N-methyl-N-nitrosourea (MNU) and aflatoxin B(1)-8,9-epoxide (AFB(1)-8,9-epoxide). The results suggest that ENPP should be classified as a mutagenic compound and a potential carcinogen.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Protease de HIV
/
Adutos de DNA
/
Glutationa Transferase
/
Mutagênicos
/
Nitrofenóis
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos