Molecular interactions between adriamycin and x-ray damage in mammalian tumor cells

The effect of the anthracycline antibiotic, Adriamycin (Ad), on the sedimentation properties of pre-labelled mammalian DNA has been studied. Ad induces DNA degradation in vivo in both excision repair-competent (HeLa and Me-180) cells and in excision repair-deficient (REQ) cells. When X-irradiated cells are exposed to Ad during the period of repair of DNA single-strand breaks, small numbers of residual breaks persist following completion of repair. These are attributable to those induced by Ad alone. The effects of Ad and X-rays therefore appear to be similar and additive. No clear-cut evidence that Ad can inhibit the repair of X-ray-induced DNA single-strand breakage was found. Ad also induced the formation of DNA double-strand breaks and inhibits the repair of X-ray-induced base damage (repair replication). The induction of DNA strand breakage may be responsible for Ad cell toxicity and may contribute to its capacity to enhance primary X-irradiation damage when the two types of lesions co-exist.