title: Effect of the dibenzylbutyrolactone lignan (-)-hinokinin on doxorubicin and methyl methanesulfonate clastogenicity in V79 Chinese hamster lung fibroblasts.
abstract: The dibenzylbutyrolactone lignan (-)-hinokinin (HK) was obtained by partial synthesis from (-)-cubebin, isolated from the dry seeds of the pepper, Piper cubeba. In view of the trypanocidal activity of HK and its potential as a lead compound for drug development, evaluation of its possible genotoxic activity is required. We have tested HK for possible genotoxicity and evaluated the compound's effect on the activity of the clastogens doxorubicin (DXR) and methyl methanesulfonate (MMS) in the micronucleus (MN) assay with Chinese hamster lung fibroblast V79 cells. HK alone did not induce MN, at concentrations up to 128microM. In combined treatments, HK reduced the frequency of MN induced by MMS. With respect to DXR, HK exerted a protective effect at lower concentrations, but at higher concentrations it potentiated DXR clastogenicity.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista Júlio de Mesquita Filho, Rodovia Araraquara-Jaú Km 1, 14801-902 Araraquara, São Paulo, Brazil.
authors.forename: Flávia Aparecida
authors.initials: FA
authors.lastname: Resende
authors.forename: Iara Maluf
authors.initials: IM
authors.lastname: Tomazella
authors.forename: Lilian Cristina
authors.initials: LC
authors.lastname: Barbosa
authors.forename: Marina
authors.initials: M
authors.lastname: Ponce
authors.forename: Ricardo Andrade
authors.initials: RA
authors.lastname: Furtado
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Pereira
authors.forename: Jairo Kenupp
authors.initials: JK
authors.lastname: Bastos
authors.forename: Márcio Luís
authors.initials: ML
authors.lastname: Andrade E Silva
authors.forename: Denise Crispim
authors.initials: DC
authors.lastname: Tavares
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D052117:Benzodioxoles; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004149:Dioxoles / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D005347:Fibroblasts / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology / Q000633:toxicity*; D008168:Lung / Q000187:drug effects; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*
chemical_list: D052117:Benzodioxoles; D004149:Dioxoles; D017705:Lignans; D009153:Mutagens; C475934:hinokinin; D004317:Doxorubicin; D008741:Methyl Methanesulfonate; D015107:4-Butyrolactone