Utility of <i>in vitro</i> assay data in predicting non-genotoxic carcinogenicity of chemicals by read-across
-
- MIZUNO Kosuke
- School of Pharmaceutical Sciences, University of Shizuoka
-
- HARAKAWA Yu
- School of Pharmaceutical Sciences, University of Shizuoka
-
- TAKESHITA Jun-ichi
- School of Pharmaceutical Sciences, University of Shizuoka National Institute of Advanced Industrial Science (AIST)and Technology
-
- HOSAKA Takuomi
- School of Pharmaceutical Sciences, University of Shizuoka
-
- SHIZU Ryota
- School of Pharmaceutical Sciences, University of Shizuoka
-
- YOSHINARI Kouichi
- School of Pharmaceutical Sciences, University of Shizuoka
Bibliographic Information
- Other Title
-
- リードアクロスによる化学物質の非遺伝毒性発がん性予測におけるインビトロ試験データの有用性
Abstract
<p>Development of alternative methods to rat carcinogenicity tests is highly demanded, but it remains very difficult. This study aimed to establish a method for predicting non-genotoxic carcinogenicity by read-across using molecular descriptors and in vitro assay data. From the results of 2-year rat carcinogenicity tests of agrochemicals published by the Food Safety Commission of Japan, we selected 80 carcinogens that cause benign or malignant tumors in liver, thyroid, testis, uterus, ovary, breast, nasal cavity, stomach, or bladder/urethra and 46 non-carcinogens that showed no carcinogenicity in these organs, and subjected these chemicals to various cytotoxicity tests in HepG2 cells and reporter assays for several nuclear receptors. Analyses using Fisher's exact test demonstrated significant associations between thyroid tumor and PXR activation, testicular tumor and AHR activation, stomach tumor and changes in GSH levels, and bladder/urethra tumor and AHR activation. Then, read-across prediction for these 4 types of tumors were performed using neighboring substances selected based on Euclidean distance between substances calculated using alvaDesc molecular descriptors, with or without stratification of the test substances by in vitro assay results. The results indicated that the stratification improved prediction accuracy (concordance rate: 0.571-0.921) compared to the accuracy based on descriptors alone (concordance rate: 0.421-0.556), suggesting that in vitro assay results are useful for read-across prediction of non-genotoxic carcinogenicity.</p>
Journal
-
- Annual Meeting of the Japanese Society of Toxicology
-
Annual Meeting of the Japanese Society of Toxicology 50.1 (0), P1-104S-, 2023
The Japanese Society of Toxicology
- Tweet
Details 詳細情報について
-
- CRID
- 1390017920607954688
-
- Text Lang
- ja
-
- Data Source
-
- JaLC
-
- Abstract License Flag
- Disallowed