We have used a grating microspectrofluorometer equipped with phase and fluorescence microscopy to study the intracellular localization and processing of fluorescent compounds that are not part of the natural cell chemistry (xenobiotics) and of fluorescent carcinogens. Our topographic and spectral observations, in conjunction with ultrastructural analysis, lead to the hypothesis of a dynamically organized multiorganelle complex involved in the cell's detoxification processes and possible protection of the cell's genetic apparatus. Our studies with quinacrine derivatives and benzo(a)pyrene suggest that the organelle complex involves the endoplasmic reticulum, the Golgi apparatus, the lysosymes, and the nuclear membrane, with a fine microchannel network interconnecting the different organelles. We have indications that there is not only a trapping of fluorescent carcinogens in the cytoplasmic components of the complex but also a possible 'nuclear pump' (powered by the substrates of the hexose monophosphate shunt pathway) involved in ejection of xenobiotics from the nucleus. The instrumental performance allows the in situ pixel-by-pixel study of extranuclear and nuclear energy metabolism related to these processes in parallel to the blue and red spectral shifts associated with metabolites spectra at different excitation wavelengths in human fibroblasts and rat liver cells allows the application of multivariate statisticaly methods to analyze multicomponent spectra. Elucidation of mechanisms involved in the organization and activity of the organelle complex is relevant to the interpretation of drug sensitivity or resistance and should result in better targeting of cancer chemotherapeutics and gene modifiers toward their expected sites of action.
|Number of pages||10|
|State||Published - Mar 1 1989|
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