Ploidy and karyotype of hepatocytes isolated from enzyme-altered foci in two different protocols of multistage hepatocarcinogenesis in the rat.

The ploidy and karyotypes of hepatocytes isolated from the livers of rats subjected to the protocols of Peraino et al. and of Solt and Farber were determined by the examination of such cells in primary culture. A study of 100 or more metaphases from each of five rats on each protocol revealed that 75-80% of gamma-glutamyltranspeptidase-positive (GGT+) hepatocytes isolated from livers of rats in either protocol were diploid, whereas only 23-33% of GGT- cells were diploid. Fifty percent or more of the karyotypes of hepatocytes from livers of rats receiving the Solt-Farber protocol exhibited one or more chromosomal breaks, whereas hepatocytes from livers of rats subjected to the Peraino protocol showed no increase in chromosomal breakage over that in normal controls. These studies demonstrate that the majority of GGT+ cells from altered hepatic foci are diploid and that the greater toxicity of the Solt-Farber protocol over that of Peraino is correlated with marked chromosomal breakage of GGT+ hepatocytes.