Synergistic effect of DAPI and thymidylate stress conditions on the induction of common fragile sites

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Abstract
When supplied to human leukocytes grown in complete medium (RPMI 1640), DAPI, a nonintercalating compound specific for the AT bases of DNA, induces the appearance of three common fragile sites (CFRA) mapped at 1q42, 2q31, and 7p22. The same treatment with DAPI in a medium deficient in folic acid and thymidine (199 M) considerably increases the expression of these sites and induces the appearance of a further 16 CFRA sites at 1q24, 2p25, 4pl6, 4q25, 5pl5.3, 6p21.3, 6p25, 6q13, 9p24, 16pl3.3, 16q23, 17q21, 18q23, 20ql3.1, 21q21, and Xq28. The results point to the existence of a synergism between DAPI and thymidylate-stress culture conditions in inducing site-specific chromosome damage. The results also agree with the hypothesis that DAPI-induced CFRA sites are DNA late-replicating chromosomal areas rich in AT bases.