PMID- 31326036
OWN - NLM
STAT- MEDLINE
DCOM- 20200302
LR  - 20210920
IS  - 1879-3592 (Electronic)
IS  - 1383-5718 (Linking)
VI  - 844
DP  - 2019 Aug
TI  - Evaluation of a 28-day repeated-dose micronucleus test in rat glandular stomach, 
      colon, and liver using gastrointestinal tract-targeted genotoxic-carcinogens and 
      non-carcinogens.
PG  - 62-68
LID - S1383-5718(19)30036-1 [pii]
LID - 10.1016/j.mrgentox.2019.05.008 [doi]
AB  - The usefulness of the rat repeated-dose liver and gastrointestinal (GI) tract 
      micronucleus (MN) tests to detect site-specific carcinogens has been shown 
      previously using 22 chemicals in a study conducted by the Mammalian Mutagenicity 
      Study group in the Japanese Environmental Mutagen Society. However, in the 6th 
      International Workshop on Genotoxicity Testing, the need for further data to 
      identify the sensitivity and specificity of the GI tract MN test and the 
      specificity of the liver MN test, for the purpose of regulatory use, was 
      mentioned. In the present study, we conducted additional studies to validate the 
      performance of the 28-day repeated-dose GI tract and liver MN tests using 
      genotoxic stomach carcinogens, N-nitroso-N-methylurea (MNU) and 
      N-methyl-N-nitrosourethane (NMUT); genotoxic colon carcinogen, 
      2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine hydrochloride (PhIP), and 
      non-carcinogens, sodium chloride, sucrose, and amaranth. Male Crl:CD (SD) rats 
      were administered with each chemical by oral gavage for 28 days and the 
      micronucleated cell frequencies in the glandular stomach, colon, and liver were 
      monitored. MNU and NMUT showed positive results in the glandular stomach, and 
      PhIP did so in the colon. These carcinogens showed negative results in the liver, 
      which is not a target organ for these chemicals. Negative results were obtained 
      for all three non-carcinogens in the glandular stomach, colon, and liver. 
      Therefore, it was shown that the glandular stomach and colon MN tests with 28-day 
      repeated-dose regimen have a good sensitivity for detecting genotoxic GI tract 
      carcinogens as positive and have a good specificity to determined non-carcinogens 
      as negative. The negative results with these six chemicals in the liver provide 
      additional evidence supporting the good specificity of the 28-day repeated-dose 
      liver MN test.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Okada, Emiko
AU  - Okada E
AD  - Yakult Central Institute, Yakult Honsha Co., Ltd, 5-11 Izumi, Kunitachi-shi, 
      Tokyo 186-8650, Japan. Electronic address: emiko-okada@yakult.co.jp.
FAU - Fujiishi, Yohei
AU  - Fujiishi Y
AD  - Yakult Central Institute, Yakult Honsha Co., Ltd, 5-11 Izumi, Kunitachi-shi, 
      Tokyo 186-8650, Japan.
FAU - Narumi, Kazunori
AU  - Narumi K
AD  - Yakult Central Institute, Yakult Honsha Co., Ltd, 5-11 Izumi, Kunitachi-shi, 
      Tokyo 186-8650, Japan.
FAU - Kado, Shoichi
AU  - Kado S
AD  - Yakult Central Institute, Yakult Honsha Co., Ltd, 5-11 Izumi, Kunitachi-shi, 
      Tokyo 186-8650, Japan.
FAU - Ohyama, Wakako
AU  - Ohyama W
AD  - Yakult Central Institute, Yakult Honsha Co., Ltd, 5-11 Izumi, Kunitachi-shi, 
      Tokyo 186-8650, Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20190519
PL  - Netherlands
TA  - Mutat Res Genet Toxicol Environ Mutagen
JT  - Mutation research. Genetic toxicology and environmental mutagenesis
JID - 101632149
RN  - 0 (Carcinogens)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Bone Marrow/*drug effects
MH  - Carcinogens/administration & dosage/*toxicity
MH  - Colon/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Hepatocytes/drug effects
MH  - Liver/*drug effects
MH  - Male
MH  - Micronucleus Tests/*methods
MH  - Organ Specificity
MH  - Rats
MH  - Sensitivity and Specificity
MH  - Stomach/*drug effects
OTO - NOTNLM
OT  - Colon
OT  - Gastrointestinal tract
OT  - Glandular stomach
OT  - Liver
OT  - Micronucleus test
OT  - Rat 28-day repeated-dose study
EDAT- 2019/07/22 06:00
MHDA- 2020/03/03 06:00
CRDT- 2019/07/22 06:00
PHST- 2019/02/06 00:00 [received]
PHST- 2019/05/17 00:00 [revised]
PHST- 2019/05/17 00:00 [accepted]
PHST- 2019/07/22 06:00 [entrez]
PHST- 2019/07/22 06:00 [pubmed]
PHST- 2020/03/03 06:00 [medline]
AID - S1383-5718(19)30036-1 [pii]
AID - 10.1016/j.mrgentox.2019.05.008 [doi]
PST - ppublish
SO  - Mutat Res Genet Toxicol Environ Mutagen. 2019 Aug;844:62-68. doi: 
      10.1016/j.mrgentox.2019.05.008. Epub 2019 May 19.