DNA accessible to dye-binding, resistance of nuclear chro matin to extraction of non-histone and histone proteins, and resistance of DNA to heat denaturation. These descnip

changes in chromatin at the molecular level, as well as differences in quantity of DNA. Techniques have been de vised to translate these features into machine-readable form, using the metachromatic fluorescent dye acnidine orange as a molecular probe of chromatin structure. The cells are prepared and stained in suspension and are mea sured individually at rates of several hundred/sec by means of a computer-interfaced, multipararneter flow cytorneter. From the measurements it is possible to determine a num ben of descriptors, including: nuclear and cellular size, quantitative values of DNA and RNA per cell, “unblocked― DNA accessible to dye-binding, resistance of nuclear chro matin to extraction of non-histone and histone proteins, and resistance of DNA to heat denaturation. These descnip tons have been used in model cell systems to classify prolif erating lymphocytes in G, G1, 5, and G2 + M phases of the cycle and to distinguish mitotic from interphase nuclei. In bladder cell cultures, differences in chrornatin structure have been demonstrated by heat denaturation of cells that could not be distinguished by measurements of total DNA per cell.