EXCLUSION OF SPECIFIC HUMAN-CHROMOSOMES INTO MICRONUCLEI BY 5-AZACYTIDINE TREATMENT OF LYMPHOCYTE-CULTURES

Lymphocyte cultures of a male proband were treated with 5-azacytidine. This cytidine analogue induces distinct undercondensation in the heterochromatic regions of chromosomes 1, 9, 15, 16, and Y and increases the frequency of micronuclei formation. In order to analyze the chromosomal content of these micronuclei, in situ hybridizations with biotinylated probes specific for chromosomes 1, 9, 15, 16, and Y were performed. Probes for chromosomes 11, 17, and X were used as controls. Each of 5000 hybridized cell nuclei was scored for associated micronuclei, and signal distribution was documented. In preparations hybridized with probes detecting the 5-azacytidine-sensitive chromosomes a significant fraction of micronuclei showed hybridizations. In contrast, micronuclei in preparations probed for chromosomes 11, 17, and X lacked hybridization signals. The results suggest that in 5-azacytidine-treated cultures the 5-azacytidine-sensitive chromosomes are preferentially excluded into the micronuclei. (C) 1994 Academic Press, Inc.