[Expression of new fragile sites detected in lymphoproliferative processes]

Fragile sites are specific chromosomal sites prone to breakage and rearrangements and they are probably related with cancer development. Fragile sites expression induced by 5-fluorodeoxyuridine (FudR) or 5-bromodeoxyuridine (BrdU) was analyzed in 4 healthy individuals and 4 patients affected with lymphoproliferative disorders: one Hodgkin's disease, one mycosis fungoides and two chronic lymphoproliferative disorders. Three standard peripheral lymphocyte cultures with F-10 medium and 5% of fetal calf serum were set up for each individual. For fragile sites induction, 10 micrograms/mL FudR or 50 micrograms/mL BrdU were added 24 hr or 6 hr before harvest. Standard and sequential G banded metaphases were studied for each individual and treatment. Quantitative analysis showed a low incidence of acentric fragments, dicentric, tri- or quadriradials, while gaps and breaks were more frequently observed. Chromosome or chromatid type aberrations were compared, showing similar values in all non-treated cultures. Chromosome type aberrations were increased in patients and controls treated cultures. Patient cultures treated by FudR presented a threefold increase of chromosome type alterations respect to chromatid ones. Moreover, chromosome breaks showed a twofold increase in patient treated cultures respect to control ones. The high number of chromosome breaks detected in these cases could be associated with an increased chromosome instability in cancer patients. Twenty common fragile sites (c-fra) were identified with sequential G banding. Patients and controls individuals have expressed 14 c-fra. Eleven of them were induced, in different proportions, by both chemical agents, showing that fragile sites share a structural homology in DNA.(ABSTRACT TRUNCATED AT 250 WORDS)