CHEMICAL INDUCTION OF SISTER-CHROMATID EXCHANGE AT FRAGILE SITES

Chromosomal breakage was studied for its correlation to sister chromat id exchange (SCE) in cultured peripheral blood lymphocytes from normal individuals following treatment with different fragile site- and brea kage-inducing chemicals. The average SCE per cell was similar for cult ures untreated or treated with fluorodeoxyuridine (FdU), caffeine, and aphidicolin (APC) (6.5 SCE), but elevated with mitomycin C (MMC) (46. 5 SCE). About half of the breaks induced with caffeine and FdU were at fragile sites, with fewer than 10% accompanied by SCE. Forty percent of MMC-induced breaks were at fragile sites, of which 47% had SCE. APC induced 68% breaks at fragile sites, of which 44% were associated wit h SCE. fragile sites induced at >4% included 3p14, 6q26, 7q22, and 16q 23. The 3p14 fragile site was induced by all chemicals except caffeine . The different frequency in induction of fragile sites and their asso ciation with SCE by the chemicals tested suggest that they are related to different mechanisms of induction which may be dependent upon nucl eotide content.