PMID- 15251178
OWN - NLM
STAT- MEDLINE
DCOM- 20050228
LR  - 20131121
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 18
IP  - 5
DP  - 2004 Oct
TI  - In vitro antigenotoxic potential of acitretin in human lymphocytes treated with 
      the antineoplastic alkylating agent ASE (NSC-71964).
PG  - 609-16
AB  - 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.
FAU - Stephanou, G
AU  - Stephanou G
AD  - Department of Biology, Division of Genetics Cell and Developmental Biology, 
      University of Patras, Rion, 26500 Patras, Greece. geosteph@biology.upatras.gr
FAU - Andrianopoulos, C
AU  - Andrianopoulos C
FAU - Tyrakis, M
AU  - Tyrakis M
FAU - Konti, M
AU  - Konti M
FAU - Demopoulos, N A
AU  - Demopoulos NA
FAU - Tsambaos, D
AU  - Tsambaos D
LA  - eng
PT  - Journal Article
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Antimutagenic Agents)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Aza Compounds)
RN  - 0 (Azasteroids)
RN  - 0 (Drug Combinations)
RN  - 0 (Keratolytic Agents)
RN  - 0 (Nitrogen Mustard Compounds)
RN  - 43000-65-3 (NSC 290205)
RN  - LCH760E9T7 (Acitretin)
SB  - IM
MH  - Acitretin/*pharmacology
MH  - Adult
MH  - Antimutagenic Agents/*pharmacology
MH  - Antineoplastic Agents/*toxicity
MH  - Aza Compounds/*toxicity
MH  - Azasteroids/*pharmacology
MH  - Cell Cycle/drug effects
MH  - Drug Combinations
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Keratolytic Agents/*pharmacology
MH  - Lymphocytes/*drug effects
MH  - Male
MH  - Micronucleus Tests
MH  - Nitrogen Mustard Compounds/*pharmacology
MH  - Sister Chromatid Exchange
EDAT- 2004/07/15 05:00
MHDA- 2005/03/01 09:00
CRDT- 2004/07/15 05:00
PHST- 2003/10/25 00:00 [received]
PHST- 2004/02/06 00:00 [accepted]
PHST- 2004/07/15 05:00 [pubmed]
PHST- 2005/03/01 09:00 [medline]
PHST- 2004/07/15 05:00 [entrez]
AID - S0887233304000347 [pii]
AID - 10.1016/j.tiv.2004.02.005 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2004 Oct;18(5):609-16. doi: 10.1016/j.tiv.2004.02.005.