HYPERSENSITIVITY OF LYMPHOBLASTOID LINES DERIVED FROM ATAXIA-TELANGIECTASIA PATIENTS TO THE INDUCTION OF CHROMOSOMAL-ABERRATIONS BY ETOPOSIDE (VP-16)

Mammalian DNA topoisomerase II represents the cellular target of many antitumor drugs, such as epipodophyllotoxin VP-16 (etoposide). The mec hanism by which VP-16 exerts its cytotoxic and antineoplastic actions has not yet been firmly established, although the unique correlation b etween sensitivity to ionizing radiation and to topoisomerase II inhib itors suggest the involvement of DNA double-strand breaks. In the pres ent study we analyzed the chromosomal sensitivity of lymphoblastoid ce ll lines derived from ataxia telangiectasia (AT) patients to low conce ntrations of the drug. Our results indicate that AT derived cells are hypersensitive to the clastogenic activity of VP-16 either when the dr ug is present for the whole duration of the cell cycle or specifically in the G2 phase, confirming that the induction of DNA double strand b reaks, to which AT cells seem typically sensitive, could have an impor tant role in the biological activity of VP-16.