| Two human cell lines cultured in vitro, a pre-B cell FLEB14 and a B-cell AHH-1 were treated with different concentrations of 5-azacytidine (5-azaC), N-methyl-N{dollar}spprime{dollar}-nitro-N-nitrosoguanidine (MNNG), 1-{dollar}beta{dollar}-D-arabinofuranosylcytosine (araC) and potassium dichromate {dollar}rm(Ksb2Crsb2,Osb7),{dollar} to induce chromosomal aberrations. Cytotoxicity induced by these genotoxins was evaluated. Chromosomal abnormalities detected by G banding at cytogenetic level included: chromosome gaps, chromosome breaks, translocations, rings, additions, marker chromosomes, figures (multibranched chromosomes) and isochromosomes.; FLEB14 cells treated with the hypomethylating agent 5-azaC gave unusual chromosome abnormalities involving preferentially the pericentromeric region of chromosome 1. These abnormalities are similar to the cytogenetic diagnostic features reported in patients with immunodeficiency, centromeric heterochromatin instability, and facial anomalies (ICF) syndrome. The evidence indicates that the chromosome heterochromatic regions involved in these aberrations are normally hypomethylated in cultured ICF lymphoblasts. Aberrations seen in this study have also been frequently reported in breast cancer. Preferential formation of chromosome 1 anomalies involving the vicinity of the centromere was also seen in AHH-l cells treated with 5-azaC, but not so frequently as in FLEB 14 cells. The preferential rearrangement of the pericentromeric heterochromatin of chromosome 1 in FLEB 14 cells was induced with 5-azaC and not detected with MNNG, araC, or {dollar}rm Ksb2Crsb2Osb7,{dollar} which alter DNA in various ways but do not cause hypomethylation. Thus DNA hypomethylation may be the common factor that links the induction of a distinct set of chromosome aberrations in FLEB14 cells in this study with similar chromosomal abnormalities in ICF syndrome cells and breast cancer. |
