High-accuracy Prediction of Carcinogenicity by Global Quantitative Analysis of Post-translational Modifications in a 28-Day In Vivo Rat Study

Cancer Genomics - Proteomics

MASARU SEKIJIMA¹  YOSHIKUNI YAKABE⁴  KOICHI SAITO²  TOMOYUKI SHIRAI⁵  HIDENORI YAMANAKA⁴  HISAYA SATO³ 

[1] ashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., Ibarakiashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., Ibarakiashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., Ibaraki;nvironmental Health Science Laboratory, Sumitomo Chemical Co. Ltd, Osakanvironmental Health Science Laboratory, Sumitomo Chemical Co. Ltd, Osakanvironmental Health Science Laboratory, Sumitomo Chemical Co. Ltd, Osaka;okyo University of Agriculture and Technology, Tokyookyo University of Agriculture and Technology, Tokyookyo University of Agriculture and Technology, Tokyo;hemicals Assessment Center, Chemicals Evaluation and Research Institute, Saitamahemicals Assessment Center, Chemicals Evaluation and Research Institute, Saitamahemicals Assessment Center, Chemicals Evaluation and Research Institute, Saitama;agoya City University Graduate School of Medical Sciences, Nagoya, Japanagoya City University Graduate School of Medical Sciences, Nagoya, Japanagoya City University Graduate School of Medical Sciences, Nagoya, Japan

关键词: 2D-DIGE;    post-translational modifications;    quantitative analysis;    rat liver proteins;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

A global quantitative analysis of post-translational modifications (PTMs) of distinct proteins was executed at the proteomic level using two-dimensional fluorescence differential gel electrophoresis. We evaluated the effects of 66 chemical compounds, including 15 genotoxic carcinogens, 28 non-genotoxic carcinogens, and 23 non-carcinogens, in the male F344 rat liver in a 28-day repeated dose study. In the master gel of rat liver protein, we identified 728 spots by hybrid quadrupole time-of-flight mass spectrometry. They collapsed into 356 distinct proteins. Of these, 126 were represented by two or more spots in the 2-D gel. We calculated the logarithmic ratio of volume changes of all 1028 combinations generated from 126 proteins and investigated the relevance to carcinogenicity. This quantitative proteomic study revealed the existence of several PTMs characteristic of carcinogens that may play an important role in early stage of carcinogenicity. Prediction of carcinogenicity from PTM data gave a higher concordance (92.4%) than prediction from protein expression data (74.2%). This novel approach holds great promise as a way of revealing the roles of charge modifications and molecular weight variations of proteins in biological processes.

【 授权许可】

Unknown