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

Overview

Journal Front Genet

Date 2021 Dec 6

PMID 34868254

Citations 1

Authors

Masami Komiya

Rikako Ishigamori

Mie Naruse

Masako Ochiai

Noriyuki Miyoshi

Toshio Imai

Yukari Totsuka

Affiliations

Soon will be listed here.

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 mimicking system, we prepared murine colonic/pulmonary organoids from 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-)pyridine (PhIP) and acrylamide (AA)-in the presence of metabolic activation systems, mutation frequencies (MFs) occurring in the 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 mutagenicity in 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 . 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.

Citing Articles

Assessment of the genotoxicity of acrylamide.

Benford D, Bignami M, Chipman J, Bordajandi L EFSA J. 2022; 20(5):e07293.

PMID: 35540797 PMC: 9069548. DOI: 10.2903/j.efsa.2022.7293.

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