FRAGILE SITES AT THE CENTROMERE OF CHINESE-HAMSTER CHROMOSOMES - A POSSIBLE MECHANISM OF CHROMOSOME LOSS

On the basis of our previous observations showing that fragile sites ( FS) mapped essentially in the centromeric regions of Chinese hamster c hromosomes, we consider the possibility that the presence of FS at the centromere might be a sourer of chromosome loss. In this model a cent romeric FS causes a centromeric break giving rise to two chromosome ar ms which could be lost or maintained with different consequences on th e ploidy of daughter cells. To test this hypothesis, Chinese hamster c ells have been treated both with N-methyl-N-nitrosourea (MNU), a mutag enic agent which also induces aneuploidy, and vinblastin (VBL), a purl aneugen, used as a control compound, which is supposed not to interac t with DNA. The results show that MNU induces the formation of translo cated and/or truncated chromosomes, on the contrary VBL is not able to induce chromosome rearrangements. The sites most involved in MNU-indu ced breaks are the centromeric regions of chromosomes where FS are als o present. These breaks cause essentially the loss of one chromosome a rm, so that the resulting cells are numerically diploid but presenting partial monosomies. The implications of these results are discussed. (C) 1998 Elsevier Science B.V.