ELSEVIER CANCER LETTERS Cancer Letters 110 (1996) 35-40 Characterization of normal and malignant human hepatocytes by Raman microspectroscopy Sharon R. Hawi”, William B. Campbell”, Andr6 Kajdacsy-Ballab, Robert Murphyb, Fran Adar”, Kasem Nithipatikom”,* “Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA hDepartment qf Pathology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA ‘Instruments, S.A., Inc., 3880 Park Avenue, Edison, NJ 08820, USA Received 12 August 1996; revision received 16 August 1996; accepted 22 August 1996 Abstract Raman microspectroscopy was used to characterize normal and malignant hepatocytes in both cultured cells and human liver tissues. Consistent spectral changes were observed, including intensity increases at 1040 and 1083 cm-’ with malig- nancy. A loss of intensity at 1241 cm-’ was also observed in cancer cells, but was obscured in tissues by the overlap of a 1253 cm-’ band, thought to originate from heme proteins. Normal liver tissue also differed from both the malignant tumor and its accompanying cirrhotic tissue at 1182 cm-‘. These results demonstrate the potential usefulness of Raman spectroscopy in clinical diagnosis, and investigations into the source of the observed spectral changes will provide information on the underlying mechanisms of carcinogenesis. Keywords: Raman microspectroscopy; Liver cancer; HepG2; Human hepatocytes 1. Introduction There is a growing belief that conversion of a nor- mal cell into a malignant tumor involves the malfunc- tion of protein-encoding genes, where the resultant oncogene may produce proteins in excess or insuffi- cient quantities, at inappropriate times, or of incorrect structure. Changes in protein or nucleic acid structure between normal and malignant cells may there- fore provide valuable cluesto understanding oncogen- * Corresponding author. Tel.: +l 414 4568267; fax: +l 414 2668460. esis. A non-invasive in vivo measurementof these changes that could distinguish normal and cancerous tissue would have tremendous clinical applications, perhapsaiding in the selection of lesions for biopsy analysis. As an example, Raman spectroscopy has recently shownpromise in the diagnosis of breast cancer [ 1,2] and gynecological cancers[3]. Thesestudies relied on changes in relative protein-to-lipid content between normal and diseased tissues. Fourier transform infra- red (FTIR) absorption spectroscopyhasalso revealed spectral differences between normal and malignant colon tissues [4] and cells [5], as well as between normal skin and basalcell carcinoma [6]. These dif- 0304-3835/96/$12.00 Copyright 0 1996 Elsevier Science Ireland Ltd. All rights reserved PII SO304-3835(96)04455-2