Komiya, Masami and Ishigamori, Rikako and Naruse, Mie and Ochiai, Masako and Miyoshi, Noriyuki and Imai, Toshio and Totsuka, Yukari (2021) Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids. Frontiers in Genetics, 12. ISSN 1664-8021
pubmed-zip/versions/2/package-entries/fgene-12-768781-r1/fgene-12-768781.pdf - Published Version
Download (1MB)
Abstract
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.
Item Type: | Article |
---|---|
Subjects: | Open Archive Press > Medical Science |
Depositing User: | Unnamed user with email support@openarchivepress.com |
Date Deposited: | 21 Jan 2023 06:07 |
Last Modified: | 20 Apr 2024 12:59 |
URI: | http://library.2pressrelease.co.in/id/eprint/272 |