Luc Hens

The central localization of the small and early replicating chromosomes in human diploid metaphase figures

SummaryCentromere-center distances are analyzed in 700 metaphase plates, which belong to four different samples. The descriptive analysis of the chromosome distribution shows that smaller, earlier replicating, gene-dense chromosomes are preferentially found near the metaphase plate center, surrounded by longer chromosomes which finish their replication rather late during S phase. This general pattern is highly constant in diploid metaphase samples and independent of sex, culture time, and number of individuals used in the sample. There is accumulating evidence that this overall distribution is not the result of technical artifacts.The metaphase plate data are complementary to the concept of an interphase nucleus structure in which late-replicating, genetically less active chromatin is accumulated at the periphery of the nucleus, while other, earlier replicating chromatin is connected with the intranuclear matrix.Although the currently available data should not be overinterpreted, an extension of the “bodyguard” hypothesis, which was suggested for C heterochromatin, provides a functional interpretation for these data: The peripherally localized, latereplicating genetic material protects the centrally localized euchromatin against mutagens, clastogens, and maybe also against viruses.

Chromosome distribution studies in phenyl mercury acetate exposed subjects and in age-related controls

Peripheral blood lymphocytes of phenyl mercury acetate exposed persons and a control population of the same age were cultured for 48 h. In both populations 100 metaphases were trypsin-banded and caryotyped. The relative position of the metaphase chromosomes was studied by means of centromere--centromere distances (delta2) and centromere--metaphase centre distances (d2) obtained by computer-aided mathematical transformation of the individual metaphase coordinates. By comparing both investigated cell populations we mainly observed that the chromosome combinations which statistically differ in mercury-exposed workers from the controls show an increase of centromere-centromere distances after mercury exposure. From the data we may suggest that phenyl mercury acetate influences at first the position of particular chromosomes; especially D-group chromosomes which are involved in nucleolus organisation. This may be due to a greater density of SH-wearing molecules in that region or to a possible inhibition of specific enzymes regulating the nucleolar activity. The exposure level is however too low to allow definite conclusions in this respect.

Comparative in vitro cytogenetic studies in mercury-exposed human lymphocytes

As part of a long-term cytogenetic research project on mercury, we studied the in vitro clastogenic capacity of HgCl2 and CH3HgCl as well as their influence on chromosome segregation by means of a computer-aided chromosome distribution study in metaphase plates. As in other in vitro studies published elsewhere, we exposed human peripheral blood lymphocytes to different concentrations of the mercury compound during a limited period of the pre-DNA synthetic stage (G1-S) or from that stage up to mitosis (G1-M). For both exposure periods and both mercury compounds we observed a rather important clastogenic effect as well as a dissociation of the (normally highly associated) acrocentrics. The results do indicate, in conjunction with previously published data, that mercury compounds alter the chromosome segregation at lower concentrations than those observed for clastogenicity. Moreover, the effects on chromosome segregation are not necessarily due to binding to spindle proteins. Binding to--and inactivation of RNA polymerase I may for example be another mechanism of action which is more important for the inorganic form of mercury than for the organic form.