title: Human sulfotransferase 1A1-dependent mutagenicity of 12-hydroxy-nevirapine: the missing link?
abstract: Nevirapine (NVP) is a frequently used anti-HIV drug. Despite its efficacy, NVP has been associated with serious skin and liver injuries in exposed patients and with increased incidences of hepatoneoplasias in rodents. Current evidence supports the involvement of reactive metabolites in the skin and liver toxicities of NVP, formed by cytochrome P450-mediated oxidations and/or subsequent phase II sulfonation. However, to date, standard in vitro genotoxicity tests have provided no evidence that NVP is either mutagenic or clastogenic. The human sulfotransferase 1A1-dependent mutagenicity of 12-hydroxy-NVP, one of the major metabolites of NVP, is demonstrated here.
authors.affiliation: Department of Genetics/CIGMH, NOVA Medical School/Faculdade Ciências Médicas, Universidade Nova de Lisboa , Rua da Junqueira 100, 1349-008 Lisbon, Portugal.
authors.forename: Michel
authors.initials: M
authors.lastname: Kranendonk
authors.forename: Mónica
authors.initials: M
authors.lastname: Alves
authors.forename: Pedro
authors.initials: P
authors.lastname: Antunes
authors.forename: José
authors.initials: J
authors.lastname: Rueff
mesh_terms: D019380:Anti-HIV Agents / Q000378:metabolism / Q000633:toxicity*; D015239:Arylsulfotransferase / Q000235:genetics / Q000378:metabolism*; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D019829:Nevirapine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D014162:Transfection
chemical_list: C000593863:12-hydroxynevirapine sulfate; D019380:Anti-HIV Agents; D009153:Mutagens; D019829:Nevirapine; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human