CONDENSATION ANOMALIES AND EXCLUSION IN MICRONUCLEI OF REARRANGED CHROMOSOMES IN HUMAN FIBROBLASTS CULTURED IN-VITRO

Anomalies of chromatin condensation, such as fragmentation, uncoiling and pulverization, were observed in XP9UV25, a xeroderma pigmentosum f ibroblast clone in which a high proportion of cells carried an end-to- end dicentric chromosome, dic (5;16) (p15.2;q24), that gives rise duri ng propagation in culture to a variety of dicentric and monocentric de rivatives. The coiling anomaly affected exclusively part of a rearrang ed chromosome, in particular the region previously involved in breakag e events. The heterochromatic 16q region, which is a preferential brea kpoint in the formation of dicentric and monocentric derivatives, was consistently the limit of the uncoiled or pulverized regions. This obs ervation suggests that the anomalous chromatin behavior could derive f rom alteration of a region relevant for the correct condensation of th e chromosome. In XP9UV25 the frequency of nuclei with associated micro nuclei increased with time in culture, in parallel with that of mitose s with dicentric chromosomes. In situ hybridization with DNA probes sp ecific for chromosomes 5 and 16 revealed hybridization signals in abou t 40% of micronuclei. Since the frequency of micronuclei is about ten times less than that of dicentrics, it is probable that only the rearr anged chromosomes undergoing coiling anomalies are excluded in micronu clei.