PMID- 28580039
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1880-7046 (Print)
IS  - 1880-7062 (Electronic)
IS  - 1880-7046 (Linking)
VI  - 39
DP  - 2017
TI  - Giemsa-stained pseudo-micronuclei in rat skin treated with vitamin D(3) analog, 
      pefcalcitol.
PG  - 17
LID - 10.1186/s41021-017-0077-9 [doi]
LID - 17
AB  - BACKGROUND: Pefcalcitol, an analog of vitamin D(3) (VD(3)), is an anti-psoriatic 
      drug candidate that is designed to achieve much higher pharmacological effects, 
      such as keratinocyte differentiation, than those of VD(3,) with fewer side 
      effects. Genotoxicity of the compound was evaluated in a rat skin micronucleus 
      (MN) test. RESULTS: In the rat skin MN test, pefcalcitol showed positive when 
      specimens were stained with Giemsa, whereas neither an in vitro chromosome 
      aberration test in CHL cells nor an in vivo bone marrow MN test in rats indicated 
      clastogenicity. To elucidate the causes of the discrepancy, the MN specimens were 
      re-stained with acridine orange (AO), a fluorescent dye specific to nucleic acid, 
      and the in vivo clastogenicity of the compound in rat skin was re-evaluated. The 
      MN-like granules that had been stained by Giemsa were not stained by AO, and 
      AO-stained specimens indicated that pefcalcitol did not increase the frequency of 
      micronucleated (MNed) cells. Histopathological evaluation suggested that the 
      MN-like granules in the epidermis were keratohyalin granules contained in 
      keratinocytes, which had highly proliferated after treatment with pefcalcitol. 
      CONCLUSIONS: Pefcalcitol was concluded to be negative in the rat skin MN test. 
      The present study demonstrated that Giemsa staining gave a misleading positive 
      result in the skin MN test, because Giemsa stained keratohyalin granules.
FAU - Takeiri, Akira
AU  - Takeiri A
AUID- ORCID: 0000-0002-5230-3850
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
FAU - Tanaka, Kenji
AU  - Tanaka K
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
FAU - Harada, Asako
AU  - Harada A
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
FAU - Matsuzaki, Kaori
AU  - Matsuzaki K
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
FAU - Yano, Mariko
AU  - Yano M
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
FAU - Motoyama, Shigeki
AU  - Motoyama S
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
FAU - Katoh, Chie
AU  - Katoh C
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
FAU - Mishima, Masayuki
AU  - Mishima M
AD  - Fuji-Gotemba Research Laboratories, Research Division, Chugai Pharmaceutical Co., 
      Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513 Japan. GRID: grid.418587.7
LA  - eng
PT  - Journal Article
DEP - 20170601
PL  - England
TA  - Genes Environ
JT  - Genes and environment : the official journal of the Japanese Environmental 
      Mutagen Society
JID - 101285347
PMC - PMC5452393
OTO - NOTNLM
OT  - Genotoxicity
OT  - Keratohyalin granule
OT  - Micronucleus
OT  - Pefcalcitol
OT  - Rat
OT  - Skin
OT  - Vitamin D3
EDAT- 2017/06/06 06:00
MHDA- 2017/06/06 06:01
PMCR- 2017/06/01
CRDT- 2017/06/06 06:00
PHST- 2016/12/15 00:00 [received]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/06/06 06:00 [entrez]
PHST- 2017/06/06 06:00 [pubmed]
PHST- 2017/06/06 06:01 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - 77 [pii]
AID - 10.1186/s41021-017-0077-9 [doi]
PST - epublish
SO  - Genes Environ. 2017 Jun 1;39:17. doi: 10.1186/s41021-017-0077-9. eCollection 
      2017.