PMID- 19551811
OWN - NLM
STAT- MEDLINE
DCOM- 20100125
LR  - 20131121
IS  - 1098-2280 (Electronic)
IS  - 0893-6692 (Linking)
VI  - 51
IP  - 1
DP  - 2010 Jan
TI  - Concordance analysis of an in vitro micronucleus screening assay and the 
      regulatory chromosome aberration assay using pharmaceutical drug candidates.
PG  - 39-47
LID - 10.1002/em.20507 [doi]
AB  - The in vitro micronucleus assay is under consideration by regulatory agencies as 
      a suitable alternative to the in vitro chromosome aberration (CA) assay. At 
      Pfizer, we utilized a non-Good Laboratory practices cytokinesis-block in vitro 
      micronucleus (CBMN) assay in CHO cells as a screen to predict the regulatory 
      outcome of the human lymphocyte CA assay, and we have retrospectively analyzed a 
      highly select set of 112 internal drug candidates to measure concordance. 
      Overall, our exploratory CBMN correctly classified 97 of 112 (86.6%) compounds in 
      the CA assay. Specificity was high with 87 of 92 (94.6%) CA negative compounds 
      correctly classified by CBMN. Sensitivity was low at 50% with 10 of 20 CA 
      positive compounds correctly classified by CBMN; this may be attributed to the 
      low number of CA positives in the select set. In an attempt to improve 
      sensitivity, we increased the number of CA positives by combining our internal 
      set with an industrial data set previously published (Miller B et al. 1997: Mutat 
      Res 392:45-59). When combined, concordance was 86.7% (143/165), specificity was 
      91.2% (114/125), and sensitivity increased to 72.5% (29/40). Because cytotoxicity 
      is considered a confounding factor of in vitro test systems, we also examined, 
      within the Pfizer data set, the influence of cytotoxicity in the CBMN assay, and 
      the results indicated that seemingly low (<50%) or excessively high (>70%) levels 
      of cytotoxicity did not significantly alter predicted CA outcome. These 
      collective analyses contribute to growing evidence that the CBMN assay is a 
      suitable regulatory option in the standard battery of genetic toxicology tests.
CI  - (c) 2009 Wiley-Liss, Inc.
FAU - Homiski, Michael L
AU  - Homiski ML
AD  - Genetic Toxicology Laboratories, Pfizer Global Research & Development, Groton, 
      Connecticut 06340, USA. michael.l.homiski@pfizer.com
FAU - Muehlbauer, Paula A
AU  - Muehlbauer PA
FAU - Dobo, Krista L
AU  - Dobo KL
FAU - Schuler, Maik J
AU  - Schuler MJ
FAU - Aubrecht, Jiri
AU  - Aubrecht J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - *Chromosome Aberrations
MH  - Cricetinae
MH  - Cricetulus
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Humans
MH  - Micronucleus Tests/*methods
MH  - Mutagenicity Tests/*methods
MH  - Retrospective Studies
EDAT- 2009/06/25 09:00
MHDA- 2010/01/26 06:00
CRDT- 2009/06/25 09:00
PHST- 2009/06/25 09:00 [entrez]
PHST- 2009/06/25 09:00 [pubmed]
PHST- 2010/01/26 06:00 [medline]
AID - 10.1002/em.20507 [doi]
PST - ppublish
SO  - Environ Mol Mutagen. 2010 Jan;51(1):39-47. doi: 10.1002/em.20507.