PMID- 27402480
OWN - NLM
STAT- MEDLINE
DCOM- 20170208
LR  - 20220409
IS  - 1879-3592 (Electronic)
IS  - 1383-5718 (Linking)
VI  - 805
DP  - 2016 Jul
TI  - The EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay: Historical 
      control data and proof of principle studies for mechanistic assay adaptations.
PG  - 25-37
LID - S1383-5718(15)30022-X [pii]
LID - 10.1016/j.mrgentox.2016.05.010 [doi]
AB  - The in vitro human reconstructed skin micronucleus (RSMN) assay in EpiDerm is a 
      promising novel animal alternative for evaluating genotoxicity of topically 
      applied chemicals. It is particularly useful for assessing cosmetic ingredients 
      that can no longer be tested using in vivo assays. To advance the use of this 
      test especially for regulatory decision-making, we have established the RSMN 
      assay in our laboratory according to Good Laboratory Practice and following the 
      principles of the OECD test guideline 487 in vitro mammalian cell micronucleus 
      test. Proficiency with the assay was established by correctly identifying 
      direct-acting genotoxins and genotoxins requiring metabolism, as well as 
      non-genotoxic/non-carcinogenic chemicals. We also report the analysis of our 
      historical control data that demonstrate vehicle control and positive control 
      values for %micronuclei in binucleated cells are in the ranges reported 
      previously. Technical issues including evaluating various solvents with both 48h 
      and 72h treatment regimens were investigated. For the first time, mechanistic 
      studies using CREST analysis revealed that the RSMN assay is suitable for 
      distinguishing aneugens and clastogens. Moreover, the assay is also suitable for 
      measuring cytokines as markers for proliferative and toxic effects of chemicals.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Roy, Shambhu
AU  - Roy S
AD  - BioReliance Corporation, 14920 Broschart Road, Rockville, MD 20850, USA. 
      Electronic address: shambhu.roy@bioreliance.com.
FAU - Kulkarni, Rohan
AU  - Kulkarni R
AD  - BioReliance Corporation, 14920 Broschart Road, Rockville, MD 20850, USA.
FAU - Hewitt, Nicola J
AU  - Hewitt NJ
AD  - SWS, Wingertstrasse 25, Erzhausen, Germany.
FAU - Aardema, Marilyn J
AU  - Aardema MJ
AD  - Marilyn Aardema Consulting LLC, 5315 Oakbrook Dr., Fairfield, OH 45014, USA.
LA  - eng
PT  - Journal Article
DEP - 20160526
PL  - Netherlands
TA  - Mutat Res Genet Toxicol Environ Mutagen
JT  - Mutation research. Genetic toxicology and environmental mutagenesis
JID - 101632149
RN  - 0 (Cytokines)
SB  - IM
MH  - Cytokines/metabolism
MH  - DNA Damage/genetics
MH  - Humans
MH  - Micronucleus Tests/*methods
MH  - Skin/*cytology/metabolism
OTO - NOTNLM
OT  - CREST
OT  - Cytokine
OT  - Dosing regimen
OT  - Historical data
OT  - Human reconstructed skin
OT  - Micronucleus
EDAT- 2016/07/13 06:00
MHDA- 2017/02/09 06:00
CRDT- 2016/07/13 06:00
PHST- 2015/11/20 00:00 [received]
PHST- 2016/05/11 00:00 [revised]
PHST- 2016/05/11 00:00 [accepted]
PHST- 2016/07/13 06:00 [entrez]
PHST- 2016/07/13 06:00 [pubmed]
PHST- 2017/02/09 06:00 [medline]
AID - S1383-5718(15)30022-X [pii]
AID - 10.1016/j.mrgentox.2016.05.010 [doi]
PST - ppublish
SO  - Mutat Res Genet Toxicol Environ Mutagen. 2016 Jul;805:25-37. doi: 
      10.1016/j.mrgentox.2016.05.010. Epub 2016 May 26.