Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: Spectroscopic changes precede morphologic changes

Background and Objective: The hamster cheek pouch carcinogenesis model, usi ng chronic treatments of dimethylbenz[alpha ]anthracene (DMBA) was used as a model system to investigate changes in epithelial tissue autofluorescence throughout the dysplasia-carcinoma sequence. Study Design/Materials and Methods: Fluorescence emission spectra were meas ured weekly from 42 DMBA-treated animals and 20 control animals at 337, 380 , and 460 nm excitation. A subset of data in which histopathology was avail able was used to develop diagnostic algorithms to separate neoplastic and n on-neoplastic tissue. The change in fluorescence intensity over time was ex amined in all samples at excitation-emission wavelength pairs identified as diagnostically useful. Results: Algorithms based on autofluorescence can separate neoplastic and n on-neoplastic tissue with 95% sensitivity and 93% specificity. Greatest con tributions to diagnostic algorithms are obtained at 380 nm excitation, and 430, 470, and 600 nm emission. Changes in fluorescence intensity are appare nt as early as 3 weeks after initial treatment with DMBA, whereas morpholog ic changes associated with dysplasia occur on average at 7.5-12.5 weeks aft er initial treatment. Conclusions: Fluorescence spectroscopy provides a potential tool to identif y biochemical changes associated with dysplasia and hyperplasia, which prec ede morphologic changes observed in histologically stained sections. (C) 20 01 Wiley-Liss, Inc.