PMID- 16364928
OWN - NLM
STAT- MEDLINE
DCOM- 20060411
LR  - 20131121
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 21
IP  - 1
DP  - 2006 Jan
TI  - Practical threshold for micronucleated reticulocyte induction observed for low 
      doses of mitomycin C, Ara-C and colchicine.
PG  - 15-20
AB  - Micronucleus induction was studied for the DNA target clastogens mitomycin C 
      (MMC) and 1-beta-D-arabinofuranosylcytosine (Ara-C), and also the non-DNA target 
      aneugen colchicine (COL) in order to evaluate the dose-response relationship at 
      very low dose levels. The acridine orange (AO) supravital staining method was 
      used for microscopy and the anti-CD71-FITC based method was used for flow 
      cytometric analysis. In the AO method, 2000 reticulocytes were analysed as 
      commonly advised, but in the flow cytometric method, 2000, 20,000, 200,000 and 
      1,000,000 reticulocytes were analysed for each sample to increase the detecting 
      power (i.e. sensitivity) of the assay. The present data show that increasing the 
      number of cells scored increases the statistical power of the assay when the cell 
      was considered as a statistical unit. Even so, statistically significant 
      differences from respective vehicle controls were not observed at the lowest dose 
      level for MMC and Ara-C, or the lower four dose levels for COL, even after one 
      million cells were analysed. When the animal was considered as a statistical 
      unit, only the top dose group for each chemical showed significant increase of 
      micronucleated reticulocytes frequency. As non-linear dose-response curves were 
      obtained for each of the three chemicals studied, these observations provide 
      evidence for the existence of a practical threshold for the DNA target clastogens 
      as well as the non-DNA target aneugen studied.
FAU - Asano, Norihide
AU  - Asano N
AD  - Toxicological Research Center, Nitto Denko Corporation, 1-1-2, Shimohozumi, 
      Ibaraki Osaka 567-8680, Japan. asanonri@nitto.co.jp
FAU - Torous, Dorothea K
AU  - Torous DK
FAU - Tometsko, Carol R
AU  - Tometsko CR
FAU - Dertinger, Stephen D
AU  - Dertinger SD
FAU - Morita, Takeshi
AU  - Morita T
FAU - Hayashi, Makoto
AU  - Hayashi M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051219
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 04079A1RDZ (Cytarabine)
RN  - 50SG953SK6 (Mitomycin)
RN  - F30N4O6XVV (Acridine Orange)
RN  - SML2Y3J35T (Colchicine)
SB  - IM
MH  - Acridine Orange
MH  - Animals
MH  - Colchicine/*administration & dosage
MH  - Cytarabine/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Male
MH  - Mice
MH  - *Micronucleus Tests
MH  - Mitomycin/*administration & dosage
MH  - Reticulocytes/cytology/*drug effects
EDAT- 2005/12/21 09:00
MHDA- 2006/04/12 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/04/12 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - gei068 [pii]
AID - 10.1093/mutage/gei068 [doi]
PST - ppublish
SO  - Mutagenesis. 2006 Jan;21(1):15-20. doi: 10.1093/mutage/gei068. Epub 2005 Dec 19.