Development of in-vitro models to elucidate mechanisms of intrinsic cellular and tissue fluorescence

摘要

Abstract: In vitro cell model systems have been used to study the mechanisms of intrinsic cellular and tissue fluorescence as a potential biomarker for cancer. Phenotypic characteristics of cancer that are different from normal tissue include changes in histoarchitecture, proliferation rates and differentiation. a nitrosmethlybenzylamine (NMBA)/rat esophageal carcinogenesis model (NMBA), a transforming growth factor beta (TGF- $beta@)ormal epithelial cell model, and a retinoic acid (RA)/multicellular tumor spheroid model (RAMTS) were used to assess fluorescence changes associated respectively with changes in histoarchitecture, proliferation rates and differentiation. A xenon based fluorescence spectrophotometer (Mediscience Corp.) was used to collect excitation and emission spectra. Two excitation scans ($lambda@Ex 200-360 nm, $lambda@Em 380 nm; $lambda@Ex 240-430 nm, $lambda@Em 450 nm) and two emission scans ($lambda@Ex 300 nm, $lambda@Em 320-580 nm; $lambda@Ex 340 nm, $lambda@Em 360-660 nm) were used to analyze the three model systems. Using the NMBA model. Differences were seen in the excitation scan ($lambda@Ex 200-360 nm, $lambda@Em 380 nm) and the emission scan ($lambda@Ex 340 nm, $lambda@Em 360-660 nm) when normal rat esophageal tissue was compared to hyperplastic and tumor tissue. In the (TGF-$beta@) model, differences were seen in the excitation scan ($lambda@Ex 240-430 nm, $lambda@Em 450 nm) when comparing proliferation slowed (TGF-$beta treated) epithelial cells to their untreated controls. In the RAMTS model, differences were seen with all four scans when RA treated multicellular tumor spheroids (nondifferentiating) were compared to untreated control cells (differentiating). The data indicate that fluorescence changes seen in these model systems may relate to changes in histoarchitecture, proliferation rates and differentiation. Their relationship to in vivo fluorescence changes seen in cancer patients remains to be elucidated.!19