Session 1: Reliability and relevance of toxicogenomics

Reliability and relevance of toxicogenomics for regulators and industry: lessons from the EU CarcinoGenomics project
PRESENTING AUTHOR: 

Professor Michael P Ryan

INSTITUTION / COMPANY : 

Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland

POSITION: 

Professor

ABSTRACT CONTENT / DETAILS: 

The overall objective of the EU CarcinoGenomics project was to develop novel in vitro cell based systems to detect and identify cancer causing compounds using transcriptomics, metabolonomics and systems biology with the ultimate aim of replacing existing genotoxicity testing and the two year rodent bioassay in the current risk assessment paradigm for carcinogens.

Human cell models for liver, kidney and lung were assessed.

Cells were exposed to a range of genotoxic carcinogens (GTX), non-genotoxic carcinogens (NGTX) and non-carcinogens (NC) and RNA extracted for transcriptomic analysis using Affymetrix gene arrays.

Different bioinformatic workflows were developed for prediction of carcinogenic hazard and assessment of inter-laboratory reproducibility.

The human kidney cell model – RPTEC/TERT 1 cells- proved the most successful with ability to identify and distinguish between GTX, NGTX and NC compounds with subsequent confirmation in a blinded inter-laboratory comparison.

Furthermore, pathway analysis revealed many similarities between human renal cancer and those occurring in this in vitro kidney model. The overall project and the lessons arising including requirements for appropriate cell biology, quality control and standard operating procedures throughout will be discussed.