The clonal nature of carcinogen-induced altered foci of gamma-glutamyl transpeptidase expression in rat liver.

The clonality of tumors has been convincingly established. Because it is generally accepted that tumor formation involves a number of steps, it is important to determine which if any of the precursors of tumors are clonal. A series of chimeric rats produced between congenic strains by morulae aggregation were used to establish the cellular composition of foci of gamma-glutamyl transpeptidase (gamma-GTP; E.C. 2.3.2.2) expression in liver following initiation with N-nitrosodiethylamine and promotion with phenobarbital. The chimeras were produced between congenic rat strains (PVG and PVG-RT1a) genetically distinguished by alleles of the major histocompatibility complex (MHC). Monoclonal antibodies directed to distinctive class I MHC alloantigens were used to detect patterns of mosaicism in the animals. The parental genotypes present in most visceral tissues could be easily distinguished by our method. Analysis of 499 enzyme-altered foci revealed that 474 were comprised solely of either PVG-RT1a or PVG cells. Some apparent mixture of cells from the two lineages was observed in 25 lesions, most of which were very small. The observed pattern of distortion of normal patch distribution clearly indicated the expanding and clonal nature of these lesions.