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Mutagenesis vol. 10 no. 3 pp. 257-260, 1995
© 1995 UK Environmental Mutagen Society/Oxford University Press

research-article

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

Lucia Gaddini1, Franca Pelliccia1,3, M. Zaira Limongi1 and Angela Rocchi1,2

1Dipartimento di Genetica e Biologia Molecolare 2Centro di Genetica Evoluzionistica del CNR, Universita ‘La Sapienza’ P. le Aldo Moro, 5, 00185 Rome, Italy

This paper reports the results of an investigation into the relationship between common fragile sites and sister chromatid exchanges (SCE). Human leukocyte cultures were grown in two different media, one complete (RPMI 1640) and one deficient in folic acid and thymidine (199M). Some of the cultures were treated with DAPI, a non-intercalating compound which binds preferentially to the AT bases of DNA and is capable of inducing fragile sites. Bromodeoxyuridine (BrdU) was added to all the cultures for SCE analysis. Chromomycin A3 was used for mapping lesions and SCEs by R-banding. A total of 400 cells was examined. The main results show that: BrdU, probably by re-equilibrating the unbalanced nucleotide pool of the 199 culture medium, interferes with the synergism between this culture medium and DAPI in inducing the expression of fragile sites; the SCE frequency per cell is not increased by DAPI in both culture media, therefore this compound does not seem to cause any damage to the DNA and seems merely to act by inhibiting the normal condensation of a subset of fragile sites that possess DAPI-specific base sequences; even in the absence of chromosomal lesions, the fragile sites are significantly preferred as SCE sites to non-fragile sites, whereas in the presence of a lesion, both fragile and non-fragile sites have the same likelihood of undergoing SCE. All this indicates that the presence of a lesion strongly favours SCE formation and that common fragile sites are probably chromosome regions preferentially damaged during the S phase.

3To whom correspondence should be addressed


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