Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids

Short-/middle-term and simple prediction studies for carcinogenesis are needed for the safety assessment of chemical substances. To establish a novel genotoxicity assay with an in vivo mimicking system, we prepared murine colonic/pulmonary organoids from gpt delta mice according to the general proce...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Masami Komiya, Rikako Ishigamori, Mie Naruse, Masako Ochiai, Noriyuki Miyoshi, Toshio Imai, Yukari Totsuka
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	murine organoids gpt delta mice PhIP acrylamide base substitution Genetics QH426-470
Acceso en línea:	https://doaj.org/article/15724e95d15948518b7d967014cde8a5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:15724e95d15948518b7d967014cde8a5
record_format	dspace
spelling	oai:doaj.org-article:15724e95d15948518b7d967014cde8a52021-11-18T18:32:40ZEstablishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids1664-802110.3389/fgene.2021.768781https://doaj.org/article/15724e95d15948518b7d967014cde8a52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.768781/fullhttps://doaj.org/toc/1664-8021Short-/middle-term and simple prediction studies for carcinogenesis are needed for the safety assessment of chemical substances. To establish a novel genotoxicity assay with an in vivo mimicking system, we prepared murine colonic/pulmonary organoids from gpt delta mice according to the general procedure using collagenase/dispase and cultured them in a 3D environment. When the organoids were exposed to foodborne carcinogens—2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) and acrylamide (AA)—in the presence of metabolic activation systems, mutation frequencies (MFs) occurring in the gpt gene dose-dependently increased. Moreover, the mutation spectrum analysis indicated predominant G:C to T:A transversion with PhIP, and A:T to C:G and A:T to T:A transversion with AA. These data correspond to those of a previous study describing in vivo mutagenicity in gpt delta mice. However, organoids derived from the liver, a non-target tissue of PhIP-carcinogenesis, also demonstrated genotoxicity with a potency comparable to colonic organoids. Organoids and PhIP were directly incubated in the presence of metabolic activation systems; therefore, there was a lack of organ specificity, as observed in vivo. Additionally, PhIP-DNA adduct levels were comparable in hepatic and colonic organoids after PhIP exposure. Taken together, the organoids prepared in the present study may be helpful to predict chemical carcinogenesis.Masami KomiyaRikako IshigamoriMie NaruseMasako OchiaiNoriyuki MiyoshiToshio ImaiToshio ImaiYukari TotsukaYukari TotsukaFrontiers Media S.A.articlemurine organoidsgpt delta micePhIPacrylamidebase substitutionGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	murine organoids gpt delta mice PhIP acrylamide base substitution Genetics QH426-470
spellingShingle	murine organoids gpt delta mice PhIP acrylamide base substitution Genetics QH426-470 Masami Komiya Rikako Ishigamori Mie Naruse Masako Ochiai Noriyuki Miyoshi Toshio Imai Toshio Imai Yukari Totsuka Yukari Totsuka Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids
description	Short-/middle-term and simple prediction studies for carcinogenesis are needed for the safety assessment of chemical substances. To establish a novel genotoxicity assay with an in vivo mimicking system, we prepared murine colonic/pulmonary organoids from gpt delta mice according to the general procedure using collagenase/dispase and cultured them in a 3D environment. When the organoids were exposed to foodborne carcinogens—2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) and acrylamide (AA)—in the presence of metabolic activation systems, mutation frequencies (MFs) occurring in the gpt gene dose-dependently increased. Moreover, the mutation spectrum analysis indicated predominant G:C to T:A transversion with PhIP, and A:T to C:G and A:T to T:A transversion with AA. These data correspond to those of a previous study describing in vivo mutagenicity in gpt delta mice. However, organoids derived from the liver, a non-target tissue of PhIP-carcinogenesis, also demonstrated genotoxicity with a potency comparable to colonic organoids. Organoids and PhIP were directly incubated in the presence of metabolic activation systems; therefore, there was a lack of organ specificity, as observed in vivo. Additionally, PhIP-DNA adduct levels were comparable in hepatic and colonic organoids after PhIP exposure. Taken together, the organoids prepared in the present study may be helpful to predict chemical carcinogenesis.
format	article
author	Masami Komiya Rikako Ishigamori Mie Naruse Masako Ochiai Noriyuki Miyoshi Toshio Imai Toshio Imai Yukari Totsuka Yukari Totsuka
author_facet	Masami Komiya Rikako Ishigamori Mie Naruse Masako Ochiai Noriyuki Miyoshi Toshio Imai Toshio Imai Yukari Totsuka Yukari Totsuka
author_sort	Masami Komiya
title	Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids
title_short	Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids
title_full	Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids
title_fullStr	Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids
title_full_unstemmed	Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids
title_sort	establishment of novel genotoxicity assay system using murine normal epithelial tissue-derived organoids
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/15724e95d15948518b7d967014cde8a5
work_keys_str_mv	AT masamikomiya establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT rikakoishigamori establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT mienaruse establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT masakoochiai establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT noriyukimiyoshi establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT toshioimai establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT toshioimai establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT yukaritotsuka establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids AT yukaritotsuka establishmentofnovelgenotoxicityassaysystemusingmurinenormalepithelialtissuederivedorganoids
_version_	1718420711012302848

Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids

Ejemplares similares