title: In vitro antigenotoxic potential of acitretin in human lymphocytes treated with the antineoplastic alkylating agent ASE (NSC-71964).
abstract: Acitretin is widely used in the systemic treatment of severe forms of psoriasis and other skin disorders. ASE, namely 3beta-hydroxy-13alpha-amino-13,17-seco-5alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloro-ethyl)amino phenylacetate (AzaSteroidalEster, NSC-71964), is an alkylating agent with antineoplastic activity and mutagenic properties. The aim of this study was to investigate the possible genotoxic and/or antigenotoxic effects of acitretin in human lymphocyte cultures in vitro, using sister chromatid exchange (SCE) and cytokinesis-blocked micronucleus (CBMN) assays. Micronucleus (MN) analysis was achieved in combination with fluorescence in situ hybridization (FISH), using an alpha-satellite DNA pancentromeric probe. It was found that acitretin alone demonstrated no clastogenic or aneugenic activity. However, simultaneous incubation of lymphocyte cultures with ASE and acitretin resulted in a reduction of ASE-induced SCEs. For MN analysis lymphocytes were treated with ASE and acitretin at 21 and 41 h after culture initiation, corresponding to G1 and G2 phases, respectively, and lasted until cell harvest. Acitretin caused a decrease in ASE-induced MN when treatment of cells started at 41 h, but exerted no effect on them when treatment started at 21 h. These findings suggest that acitretin exerts antigenotoxic effects in human lymphocyte cultures, the expression of which may be related to the cycle phase of the cells upon onset and duration of the treatment, at least as far as MN frequency is concerned.
authors.affiliation: Department of Biology, Division of Genetics Cell and Developmental Biology, University of Patras, Rion, 26500 Patras, Greece. geosteph@biology.upatras.gr
authors.forename: G
authors.initials: G
authors.lastname: Stephanou
authors.forename: C
authors.initials: C
authors.lastname: Andrianopoulos
authors.forename: M
authors.initials: M
authors.lastname: Tyrakis
authors.forename: M
authors.initials: M
authors.lastname: Konti
authors.forename: N A
authors.initials: NA
authors.lastname: Demopoulos
authors.forename: D
authors.initials: D
authors.lastname: Tsambaos
mesh_terms: D017255:Acitretin / Q000494:pharmacology*; D000328:Adult; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001372:Aza Compounds / Q000633:toxicity*; D001378:Azasteroids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004338:Drug Combinations; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007641:Keratolytic Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D012854:Sister Chromatid Exchange
chemical_list: D016587:Antimutagenic Agents; D000970:Antineoplastic Agents; D001372:Aza Compounds; D001378:Azasteroids; D004338:Drug Combinations; D007641:Keratolytic Agents; D009588:Nitrogen Mustard Compounds; C017888:NSC 290205; D017255:Acitretin