Spatiotemporal Mapping Of Fluorescence Paramaters In Single Living Cells The Cell's Detoxification Apparatus

Our studies with quinacrine and benzo(a)pyrene suggest the formation of a multiorganelle detoxification complex (MODC) involving the endoplasmic reticulum, the Golgi apparatus, the lysosomes and the nuclear membrane. We have indications that not only is there a trapping of xenobiotics in the cytoplasmic components of the MODC, but there may also be a "nuclear pump" powered by postulated nuclear bioenergetic pathways involved in the ejection of these chemicals from the nucleus. We are using the microspectrofluorometric approach to study the extranuclear/nuclear energy metabolism related to these processes, and we have extended this method to investigate, in situ, within different components of the MODC, the blue/red spectral shifts associated with metabolites of fluorescent xenobiotics. Recording of fluorescence emission spectra, at different excitation wavelengths in L cells, allows the application of multivariate statistical methods to analyze complex (multicomponent spectra). Eluciadation of mechanisms, involved in the organization and activity of the MODC, can result in better targeting of gene modifiers and DNA-intercalating cancer chemotherapeutics towards their expected sites of action.

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