INDUCTION OF CHROMOSOME-ABERRATIONS AND DELAYED GENOMIC INSTABILITY BY PHOTOCHEMICAL PROCESSES

Exponentially growing cells cultured in medium containing bromodeoxyur idine, then exposed to UVA light in the presence of the dye Hoechst 33 258, show significant levels of DNA strand breaks and base damage, Thi s dye-bromodeoxyuridine-UVA photolysis treatment is markedly cytotoxic , We now demonstrate that exposure of cells to the agents used in phot olysis leads directly to the formation of chromosome aberrations, Furt hermore, we demonstrate that this photochemical treatment induces dela yed chromosomal instability in clonal populations derived from single progenitor cells surviving photolysis, These results suggest that phot olysis-induced DNA damage leads to chromosome rearrangements that coul d account for the observed cytotoxicity, Furthermore, in those cells s urviving photolysis, the delayed effects of this treatment can be obse rved several generations after exposure and are manifested as compromi sed genomic integrity.