Genotoxic activity of chlorohydroxyfuranones in the microscale micronucleus test on mouse lymphoma cells and the unscheduled DNA synthesis assay in rat hepatocytes

Chlorohydroxyfuranones (CHFs) are mutagenic disinfection by-productsfound in chlorine-treated drinking water. In the current study,the genotoxicity of four CHFs, 3,4-dichloro-5-hydroxy-2(5H)-furanone(MCA), 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone(CMCF) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone(MX), was determined. Two in vitro assays, the microscale micronucleusassay on L5178Y mouse lymphoma cells and the unscheduled DNAsynthesis assay on a hepatocyte primary culture from FisherF344 rats, were carried out. All four CHFs demonstrated genotoxiceffects in both assays. In the two systems used, CMCF was themost genotoxic compound, followed by MCA, MX and MCF, respectively.This work was the first study of the DNA damaging propertiesof all four CHFs in two in vitro genotoxicity tests. These newdata expand the range of genetic damages induced by this groupof compounds. ² To whom correspondence should be addressed. Tel: +33 3 20 8779 14; Fax: +33 3 20 87 73 10; Email: daniel.marzin{at}pasteur-lille.fr     

Ginkgo biloba extract EGb761 reduces the development of amphetamine-induced behavioral sensitization: effects on hippocampal type II corticosteroid receptors

Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the behavioral sensitization induced by successive -amphetamine administrations (0.5 mg/kg) as estimated by increasing values of locomotor activity. EGb761 pretreatment also prevented the reduced density of [³H]dexamethasone binding sites in the dentate gyrus and the CA1 hippocampal regions of -amphetamine treated animals. These observations suggest that EGb761, by reducing glucocorticoid levels, could modulate the activity of the neuronal systems involved in the expression of the behavioral sensitization.