FREQUENT DELETION IN CHROMOSOME-4 AND DUPLICATION OF CHROMOSOME-15 INLIVER EPITHELIAL-CELLS DERIVED FROM LONG-TERM CULTURE OF C3H MOUSE HEPATOCYTES

Prolonged culture of hepatocytes isolated from mouse liver results in the spontaneous development of colonies of liver epithelial cells that can proliferate indefinitely in vitro. We established 5 such cell lin es from C3H/HeJ mice (C3H) and 22 cell lines from C3H/HeJ x C57BL/6J F -1 mice (C3B6F(1)) to investigate whether any specific karyotype alter ations may be associated with the development of such cells. These lin es retained some properties of hepatocytes as well as showing bile-duc t-cell characteristics, and comprised mainly near-diploid and/or hypot etraploid cells. Karyotypic analysis of the C3H cell lines indicated t hat most cells have loss of chromosome 4 or deletion involving the C7 portion, while at least 1 (for near-diploid cells) or 2 (for hypotetra ploid cells) copies of chromosome 4 were usually intact. In addition, gain of an extra chromosome 15 was frequently observed in these cell l ines. Analysis of the microsatellite DNA polymorphic markers in 22 C3B 6F(1) lines revealed that a majority of them showed loss of heterozygo sity (LOH) for, at least, 1 of 3 polymorphic loci on chromosome 4, but not for 2 loci on chromosomes 7 and 11. Mouse chromosomes 4 and 15, t herefore, may contain genes related to the ability of such liver epith elial cells to grow indefinitely in vitro [The locus on chromosome 4 w as designated as liver-cell immortalization (LCI) locus]. (C) 1994 Wil ey-Liss, Inc.