LOBULE-DEPENDENT ZONAL MEASUREMENT (LZM) METHOD FOR THE DETERMINATIONOF CELL-PROLIFERATION IN THE LIVER

Using the conventional method of measurement (randomly distributed fie lds) there is a risk of overlooking a biologically relevant effect due to the different zonal expression of cell proliferation. Therefore a lobule-dependent zonal measurement (LZM) method was developed that gua ranteed the independent evaluation of the hepatic zones in lobules of a comparable size. With this method, applied in a 3-month-study, a sta tistically significant increase in cell proliferation after one week ( 71 %) and a distinct increase after six weeks (49 %) and thirteen week s (32 %) of exposure could be proved, whereas the conventional method revealed after one week only a slight increase (22 %), after six weeks a distinct but not statistically significant increase (56 %) and afte r thirteen weeks even a decrease of 24 %. In comparison, the LZM-metho d revealed a panlobular increase of cell proliferation after one week of administration, that shifted to the periportal region after six and thirteen weeks representing the target zone as it was shown by electr onmicroscopy later on. Since the test substance evoked an increased tu mor incidence in both sexes in a lif-span study, the enhanced cell pro liferation, in our case especially in the periportal area, seems to be a key mechanism in tumor development. These data confirm that the, LZ M-method represents a very sensitive and stable method in the evaluati on of cell proliferation in the liver.