Interaction of GGCC sequences of DNA with anticancer dianhydrogalacticol, detected by inhibition of restriction enzyme BspI.

Abstract

Interaction of DNA with 1,2-5,6-dianhydro-galactitol (DAG, NSC 132 313), a bifunctional alkylating agent used in cancer therapy was studied. Treatment of lambda phage DNA with DAG in vitro protected some of the specific cleavage sites against the restriction enzyme BspI. The extent of protection depended on the concentration and time of DAG treatment but complete protection was not observed. Since the inactivation of the enzyme by DAG was excluded experimentally, the protection can be attributed to the binding of DAG to GGCC sequences of DNA. These experiments support the finding that guanine is the target of DNA alkylation by DAG (Institóris and Tamás, 1980). DAG treatment in vitro induced single strand breaks on DNA and this effect was also found to be concentration and time dependent.