EFFICIENCY OF A SPECIFIC ALBUMIN EXTINGUISHER LOCUS IN MONOCHROMOSOMAL HEPATOMA HYBRIDS

Fusion of hepatoma cells with cells of similar ploidy (1s) from differ ent histogenetic origin results in the systematic and stable extinctio n of hepatic traits. However, doubling the ploidy of the hepatoma pare nt (2s) leads to the formation of hybrids in which extinction is not o bserved. To establish if these dosage effects reflect, as generally th ought, the ineffectiveness of the extinguishers in 2s hepatoma-derived hybrids, the efficiency of a specific extinguisher was improved. Rat hepatoma cells (1s) stably and selectively extinguished for albumin, o wing to the presence of a single mouse fibroblast chromosome marker M1 , were fused with the original albumin producing hepatoma cells. In th e dozen independent hybrid clones isolated, the M1 chromosome was reta ined and the rat albumin gene silenced. This proves that the albumin e xtinguisher is still efficient when the number of its targets is doubl ed. However the extinction promoted by this extinguisher was not immed iate after fusion. A detailed analysis of the time course of extinctio n revealed that a precise number of cell divisions, seven, is required for the monochromosomal 2s hybrid cells to become extinguished. This phenotype was stable but reversible, loss of M1 chromosome leading to albumin expression. Moreover, the M1 part carrying the specific albumi n extinguisher locus, Tse a, was identified as mouse chromosome 3. (C) 1994 Academic Press, Inc.