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High degree of satellite association and decreased nucleolar organizer activity in cystic fibrosis subjects.

The effect of colchicine at concentrations of 0.25 X 10(-6) M, 1.0 X 10(-6) M, and 2.0 X 10(-6) M on the degree of satellite association (SA) was estimated in phytohemagglutinin-stimulated lymphocytes of individuals in the following groups: cystic fibrosis (CF) children, obligatory CF heterozygotes, control children, and control adults. In all four groups increasing colchicine concentration caused a higher degree of SA. The degree of SA differed between the two control age groups (children vs adults) only at the lowest concentration. CF patients had a significantly higher degree of SA than CF heterozygotes and than control individuals at all colchicine concentrations; CF heterozygotes had a significantly higher degree of SA than control adults at the low and intermediate concentrations. There was a strong interaction between genotype and colchicine concentration: the differences between the CF patients and the control individuals were most distinct at the intermediate concentration and between the carriers and the control individuals at the low colchicine concentration. Colchicine had no effect on the activity of the nucleolar organizer regions (NORs), as measured by the frequency of the silver-stained NORs (AgNORs), while the frequency of AgNORs in CF patients was significantly lower as compared to control individuals. Yet, the increase in the degree of SA caused by the CF mutant allele involved specifically the satellited chromosomes carrying active NORs.