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Classification of test agent-specific effects in the Syrian hamster embryo assay (pH 6.7) using infrared spectroscopy with computational analysis

Ahmadzai, Abdullah A. and Trevisan, Julio and Pang, Weiyi and Patel, Imran I. and Fullwood, Nigel J. and Bruce, Shannon W. and Pant, Kamala and Carmichael, Paul L. and Scott, Andrew D. and Martin, Francis L. (2012) Classification of test agent-specific effects in the Syrian hamster embryo assay (pH 6.7) using infrared spectroscopy with computational analysis. Mutagenesis, 27 (3). pp. 375-382. ISSN 0267-8357

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Abstract

The Syrian hamster embryo (SHE) cell transformation assay (pH 6.7) has utility in the assessment of potential chemical carcinogenicity (both genotoxic and non-genotoxic mechanisms of action). The assay uses morphological transformation as an end point and has a reported sensitivity of 87%, specificity of 83% and overall concordance of 85% with in vivo rodent bioassay data. However, the scoring of morphologically transformed SHE cells is subjective. We treated SHE cells grown on low-E reflective slides with benzo[a]pyrene, 3-methylcholanthrene, anthracene, N-nitroso-N-methylnitroguanidine, ortho-toluidine HCl, 2,4-diaminotoluene or D-mannitol for 7 days before fixation with methanol. Identified colonies were interrogated by acquiring a minimum of five infrared (IR) spectra per colony using attenuated total reflection Fourier-transform IR spectroscopy. Individual IR spectra were acquired over a spatial area of approximately 250 x 250 mu m. Resultant data were analysed using Fisher's linear discriminant analysis and feature histogram algorithms to extract classifying biomarkers of test agent-specific effects or transformation in SHE cells. Clustering of spectral points suggested co-segregation or discrimination of test agent categories based on mechanism of action. Towards transformation, unifying alterations were associated with alterations in the Amide I and Amide II peaks; these were consistently major classifying biomarkers for transformed versus non-transformed SHE cells. Our approach highlights a novel method towards objectively screening and classifying SHE cells, be it to ascertain test agent treatment based on mechanism of action or transformation.

Item Type: Article
Journal or Publication Title: Mutagenesis
Subjects: Q Science > QH Natural history > QH301 Biology
Departments: Faculty of Science and Technology > Lancaster Environment Centre
Faculty of Science and Technology > School of Computing & Communications
Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 59899
Deposited By: ep_importer_pure
Deposited On: 08 Nov 2012 13:27
Refereed?: Yes
Published?: Published
Last Modified: 10 Apr 2014 00:18
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/59899

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