Changes in Hepatocyte Ploidy in Response to Chromium, Analyzed by Computer-Assisted Microscopy

Changes in Hepatocyte Ploidy in Response to Chromium, Analyzedby Computer-Assisted Microscopy. GARRISON, J.C., BISEL, T. U.,PETERSON, P., AND UYEKJ, E. M. (1990). Fundam. Appl. Toxicol.14, 346–355. BDF1 mice were given single injections ofsodium dichromate (25 mg/kg) on an acute (6 hr to 7 days) orintermediate (2-4 weeks) basis, or multiple injections (12.5mg/kg) on a chronic (4.5 months) basis. Observed hepatic changesincluded programmed cell death (apoptosis) in the periportalregion with acute exposure and fusion of liver lobes with chronicexposure. Response to chromate exposure was measured by changein hepatocyte nuclear ploidy state (e.g., the proportion ofdiploid, tetraploid, and octaploid nuclei) based on computer-assistedimaging from histological sections. The computer-assisted imagingsystem used in this study was superior to traditional methodsbecause it (1) allows rapid ploidy determinations from histologicalmaterial and (2) can be used to collect regional information.Regional differences in ploidy were seen to occur in a consistentfashion among both control and treated animals. Nuclei adjacentto the portal triad had the lowest ploidy value (highest proportionof diploid nuclei), an intermediate value was found adjacentto the central vein, and the highest ploidy was found in themidzone. These three ploidy-based zones roughly correspond tothe three functional zones of A. M. Rappaport (1973, Microvasc.Res. 6, 212–228) and W. H. Lam-ers el 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 amongcontrol animals (all zones), with young animals (56 days) displayingrelatively low ploidy values compared to older animals (184days). 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 treatedfor longer periods of time, probably because of age-relatedfactors.