Study of the relationships between common fragile sites, chromosome breakages and sister chromatid exchanges

This paper reports the results of an investigation into therelationship between common fragile sites and sister chromatidexchanges (SCE). Human leukocyte cultures were grown in twodifferent media, one complete (RPMI 1640) and one deficientin folic acid and thymidine (199M). Some of the cultures weretreated with DAPI, a non-intercalating compound which bindspreferentially to the AT bases of DNA and is capable of inducingfragile sites. Bromodeoxyuridine (BrdU) was added to all thecultures for SCE analysis. Chromomycin A₃ was used for mappinglesions and SCEs by R-banding. A total of 400 cells was examined.The main results show that: BrdU, probably by re-equilibratingthe unbalanced nucleotide pool of the 199 culture medium, interfereswith the synergism between this culture medium and DAPI in inducingthe expression of fragile sites; the SCE frequency per cellis not increased by DAPI in both culture media, therefore thiscompound does not seem to cause any damage to the DNA and seemsmerely to act by inhibiting the normal condensation of a subsetof fragile sites that possess DAPI-specific base sequences;even in the absence of chromosomal lesions, the fragile sitesare significantly preferred as SCE sites to non-fragile sites,whereas in the presence of a lesion, both fragile and non-fragilesites have the same likelihood of undergoing SCE. All this indicatesthat the presence of a lesion strongly favours SCE formationand that common fragile sites are probably chromosome regionspreferentially damaged during the S phase. ³To whom correspondence should be addressed