Changes in hepatocyte ploidy in response to chromium, analyzed by computer-assisted microscopy

BDF1 mice were given single injections of sodium dichromate (25 mg/kg) on an acute (6 hr to 7 days) or intermediate (2-4 weeks) basis, or multiple injections (12.5 mg/kg) on a chronic (4.5 months) basis. Observed hepatic changes included programmed cell death (apoptosis) in the periportal region with acute exposure and fusion of liver lobes with chronic exposure. Response to chromate exposure was measured by change in hepatocyte nuclear ploidy state (e.g., the proportion of diploid, tetraploid, and octaploid nuclei) based on computer-assisted imaging from histological sections. The computer-assisted imaging system used in this study was superior to traditional methods because it (1) allows rapid ploidy determinations from histological material and (2) can be used to collect regional information. Regional differences in ploidy were seen to occur in a consistent fashion among both control and treated animals. Nuclei adjacent to the portal triad had the lowest ploidy value (highest proportion of diploid nuclei), an intermediate value was found adjacent to the central vein, and the highest ploidy was found in the midzone. These three ploidy-based zones roughly correspond to the three functional zones of A. M. Rappaport (1973, Microvasc. Res. 6, 212-228) and W. H. Lamers et al. W. H. Lamers, A. Hilberts, E. Furt, J. Smith, G. N. Jonges, J. F. Van Noorden, J. W. G. Janzen, R. Charles, and A. F. M. Moorman, 1989, Hepatology, 10, 72-76. Temporal changes in ploidy were seen among control animals (all zones), with young animals (56 days) displaying relatively low ploidy values compared to older animals (184 days). Chromate exposure caused increased ploidy (all zones) among animals treated on an acute basis (the youngest animals). Chromate had no apparent effect on ploidy among animals treated for longer periods of time, probably because of age-related factors.