Protease inhibitors neither damage DNA nor interfere with DNA repair or replication in human cells.

Human fibroblasts were exposed to antipain or leupeptin at concentrations up to 2.5 mM and the presence of DNA damage and repair was assayed by several different methods. These did not reveal DNA damage or repair after exposure to either antipain or leupeptin, even in the presence of rat-liver microsomal S9 mix. Antipain also had no significant effects on the repair or replication of DNA after ultraviolet or X-irradiation. The demonstrated potentiation of radiation-induced transformation of human cells and the selective killing of repair-deficient cells by antipain must therefore occur by mechanisms that do not involve direct interaction of antipain with DNA.