PMID- 10719040
OWN - NLM
STAT- MEDLINE
DCOM- 20000512
LR  - 20190513
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 15
IP  - 2
DP  - 2000 Mar
TI  - Cytokinesis-block micronucleus assay in primary human liver fibroblasts exposed 
      to griseofulvin and mitomycin C.
PG  - 143-7
AB  - Primary liver fibroblasts were applied in a cytokinesis-block micronucleus assay 
      in combination with fluorescence in situ hybridization (FISH) using two 
      protocols. In protocol A (Prot. A), cytochalasin B (Cyt B) was added at the end 
      of the treatment time directly to the medium containing the standard compounds, 
      whereas in protocol B (Prot. B) the chemical-containing medium was removed and 
      fresh medium with Cyt B was added. The study was performed using the aneugen 
      griseofulvin (GF) and the clastogen mitomycin C (MMC) as standard compounds. With 
      both protocols GF induced a significant increase in MN frequency over controls in 
      a dose-related manner at the lower concentrations tested (7.5 and 15 microg/ml). 
      At the highest dose (30 microg/ml) the aneugen effect was substantially reduced. 
      MN induction obtained with Prot. A was significantly higher ( approximately 
      3-fold) than with Prot. B at the most effective concentration. The aneugen effect 
      induced by GF did not change when different cell densities were used, but again 
      with Prot. A we obtained the highest effect. MN induced by MMC showed a dose- and 
      time-dependent increase in both protocols. In contrast to GF, the greater 
      clastogenic response induced by MMC in human liver fibroblasts was obtained with 
      Prot. B, approximately 3-fold higher than Prot. A at the most effective 
      concentration and approximately 2-fold with 24 h treatment at 0.17 microg/ml MMC. 
      With GF, the FISH data in human liver fibroblasts (80% C+MN) were fairly 
      consistent with those obtained in the rodent cell lines. In human whole blood 
      cultures, the same dose used in our experiment produced a relatively higher 
      percentage of C+MN. FISH analysis showed that MMC induced mainly MN containing 
      acentric fragments rather than whole chromosomes. In conclusion we have 
      demostrated that chemically induced genetic effects are strongly dependent on the 
      cell culture employed, treatment schedule and intra- and post-treatment 
      experimental conditions.
FAU - Nesti, C
AU  - Nesti C
AD  - Dipartimento Uomo e Ambiente, Universita' di Pisa, Via S.Giuseppe 22, and 
      Istituto di Mutagenesi e Differenziamento del CNR, Via Svezia 10, 56100 Pisa, 
      Italy.
FAU - Trippi, F
AU  - Trippi F
FAU - Scarpato, R
AU  - Scarpato R
FAU - Migliore, L
AU  - Migliore L
FAU - Turchi, G
AU  - Turchi G
LA  - eng
PT  - Journal Article
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Antifungal Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 32HRV3E3D5 (Griseofulvin)
RN  - 50SG953SK6 (Mitomycin)
RN  - 7QID3E7BG7 (Dicumarol)
SB  - IM
MH  - Antifungal Agents/pharmacology
MH  - Cells, Cultured
MH  - Chromosomes/drug effects
MH  - DNA Damage
MH  - Dicumarol/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts/*drug effects
MH  - Griseofulvin/*pharmacology
MH  - Humans
MH  - In Situ Hybridization
MH  - In Situ Hybridization, Fluorescence
MH  - Liver/*drug effects
MH  - Micronuclei, Chromosome-Defective/*drug effects
MH  - Micronucleus Tests/*methods
MH  - Mitomycin/*pharmacology
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
EDAT- 2000/03/17 09:00
MHDA- 2000/05/20 09:00
CRDT- 2000/03/17 09:00
PHST- 2000/03/17 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 2000/03/17 09:00 [entrez]
AID - 10.1093/mutage/15.2.143 [doi]
PST - ppublish
SO  - Mutagenesis. 2000 Mar;15(2):143-7. doi: 10.1093/mutage/15.2.143.