Telomere change and loss of heterozygosity of mouse primary tumors and cell lines

Abstract

Changes in the number of telomere repeat arrays were examined in mouse tumor cells. Telomeres that function for the protection of chromosomes were detected as bands and a smear by pulsed field gel electrophoresis and gel-hybridization using (TTAGGG)4, as a probe. Of eight primary tumors induced in F1 mice between C57BL/6 and C3H/He and between C57BL/6 and MSM, three showed telomere alteration, two having extra bands and one having lost several telomere bands. The others exhibited patterns similar to those of normal tissues. However, the change was detected in all four cell lines that were established from one of the tumors. One cell line was further cloned and examined. Two of the nine clones differed in the telomere pattern. The telomere change was also observed in two other cell lines, FM3A cells and nontransformed BALB3T3 cells. These results suggest that telomeres are highly mutable in tumor cells and cultured cell lines. Three of the tumors and one cell line were analyzed for loss of heterozygosity with 51 microsatellite probes covering all 19 autosomes. Also, karyotype analysis of the cell line was performed. No allelic loss was seen and chromosomal abnormality was rare, although aneuploidy and imbalance in chromosomal number were observed. Possible involvement of the telomere changes observed here in chromosome impairment is discussed.