title: Mutagenic activity and DNA adduct formation by 1, 2-epoxy-3-(p-nitrophenoxy)propane, an HIV-1 protease inhibitor and GST substrate.
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.
authors.affiliation: Department of Community and Environmental Medicine, College of Medicine, Irvine, California, 92697-1820, USA.
authors.forename: B
authors.initials: B
authors.lastname: Said
authors.forename: D C
authors.initials: DC
authors.lastname: Matsumoto
authors.forename: A K
authors.initials: AK
authors.lastname: Hamade
authors.forename: R C
authors.initials: RC
authors.lastname: Shank
mesh_terms: D002273:Carcinogens / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004852:Epoxy Compounds / Q000378:metabolism / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000494:pharmacology; D009596:Nitrophenols / Q000378:metabolism* / Q000494:pharmacology*; D012475:Salmonella / Q000235:genetics
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D004852:Epoxy Compounds; D017320:HIV Protease Inhibitors; D009153:Mutagens; D009596:Nitrophenols; D006147:Guanine; C007606:1,2-epoxy-3-(p-nitrophenoxy)propane; D005982:Glutathione Transferase