Abstract
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.
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