Developing an integrated "in vitro carcinogenicity predictive tool" utilising in vitro cell signalling and cell behaviour assessment coupled with in vitro genotoxicity data

Cancer arises due to the accumulation of multiple disparate abnormalities governing how cells control their growth. Some of these abnormalities involve the accumulation of DNA mutations, hence DNA mutagens (agents that alter DNA) are nearly always capable of inducing cancer. Therefore a traditional way to assess cancer risk of new chemical agents is merely to focus on DNA mutability. Unfortunately, this approach does not detect chemicals that cause cancer in other (non-DNA) ways. It is also not 100% accurate in detecting chemicals that do mutate DNA, and even throws up numerous false positives (wrongly classifies safe chemicals as mutagens), which require animal experiments for clarification. In this proposal we aim to develop a better approach to detecting carcinogens, by focussing on induced abnormalities in cell signals controlling cellular growth and on how cells behave by monitoring multiple cellular parameters after exposure to the test chemicals. We hypothesise that this more holistic approach will yield a better prediction of which chemicals are potential carcinogens. As this apporach is entirely in vitro (cultured cells), this could have a major impact on the use of animals in safety testing and reduce the numbers of animals needed by tens of thousands per year.

Johnson GE et al. (2014) Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment. Environ. Mol. Mutagen. doi: 10.1002/em.21870

Gollapudi BB et al. (2013) Quantitative approaches for assessing dose-response relationships in genetic toxicology studies. Environ. Mol. Mutagen. 54(1):8-18. doi: 10.1002/em.21727

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Strategic grant

Status:

Closed

Principal investigator

Professor Gareth Jenkins

Institution

Swansea University

Co-Investigator

Dr Shareen Doak
Dr George Johnson

Grant reference number

NC/K500033/1

Award date:

Apr 2012 - Sep 2015

Grant amount

£384,143