Fragile sites at the centromere of Chinese hamster chromosomes: a possible mechanism of chromosome loss

Abstract On the basis of our previous observations showing that fragile sites (FS) mapped essentially in the centromeric regions of Chinese hamster chromosomes, we consider the possibility that the presence of FS at the centromere might be a source of chromosome loss. In this model a centromeric FS causes a centromeric break giving rise to two chromosome arms which could be lost or maintained with different consequences on the ploidy of daughter cells. To test this hypothesis, Chinese hamster cells have been treated both with N -methyl- N -nitrosourea (MNU), a mutagenic agent which also induces aneuploidy, and vinblastin (VBL), a pure aneugen, used as a control compound, which is supposed not to interact with DNA. The results show that MNU induces the formation of translocated and/or truncated chromosomes, on the contrary VBL is not able to induce chromosome rearrangements. The sites most involved in MNU-induced breaks are the centromeric regions of chromosomes where FS are also present. These breaks cause essentially the loss of one chromosome arm, so that the resulting cells are numerically diploid but presenting partial monosomies. The implications of these results are discussed.