Mitonafide (5-nitro-2-(2-dimethylaminoethyl)-benzo- [de]
isoquinoline-1,3-dione hydrochloride), a new candidate as an anticancer or
antiviral agent, inhibited the incorporation of
DNA precursors into the
acid-insoluble fractions of cultured Chinese hamster ovary (CHO) cells and also into CHO cells made permeable (i.e., "permeabilized") that were supplemented with
ATP and deoxynucleoside triphosphates.
Mitonafide enhanced the degradation of previously incorporated [3H]
thymidine and increased the amount of
DNA recovered in fractions containing
single-stranded DNA after alkaline denaturation and
hydroxyapatite chromatography. At concentrations of 0.01 and 1.0 microM, respectively,
mitonafide increased the frequency of sister chromatid exchanges and
chromosome aberrations in CHO cells. The inhibition of
DNA synthesis in a permeabilized cell system suggested that
mitonafide acted on the
DNA-synthesizing apparatus without requiring metabolic conversion and interfered with
DNA synthesis independent of the cellular metabolism of
DNA precursors.
Mitonafide induced
DNA strand breaks and
chromosome abnormalities in cultured cells.