Daunorubicin-induced DNA lesions in isolated rat hepatocytes and mammary epithelial cells.

Daunorubicin, an anticancer drug, induces primarily mammary adenocarcinoma in Sprague-Dawley rats. We investigated daunorubicin-induced DNA lesions in enzymatically isolated mammary epithelial cells and hepatocytes from 7-8-week-old female Sprague-Dawley rats. Differences were observed in the type and quantity of DNA lesions in mammary epithelial cells and hepatocytes as determined by alkaline elution analysis.

Adriamycin-mediated introduction of a limited number of single-strand breaks into supercoiled DNA.

It was reported previously that Adriamycin converts form I covalently closed circular, supercoiled bacteriophage PM2 DNA to the relaxed circular form II DNA; no form III linear DNA was produced as a result of the extracellular action of Adriamycin in the presence of NADH-dehydrogenase. When form II DNA, produced by the action of Adriamycin, was treated with the BAL 31 nuclease, a single sharp DNA band after agarose gel electrophoresis indicated the presence of only full-length linear form III DNA. As one of its activities, the BAL 31 nuclease introduces a single-strand break in the complementary strand opposite a preexisting single-strand break.

Agarose gel electrophoretic analysis of damage to supercoiled DNA by adriamycin in the presence of beta-NADH dehydrogenase.

In a cell-free system, the anticancer anthracycline antibiotic adriamycin was able to convert purified covalently closed circular, superhelical, form I bacteriophage PM2 DNA to relaxed circular form II DNA in the presence of either sodium borohydride (NaBH4), NADPH cytochrome P-450 reductase or beta-NADH dehydrogenase isolated from myocardial cells. There was no detectable increase in the amount of form III linear duplex DNA formed during the reaction even at high drug concentrations. Less drug was required for the conversion of form I to form II DNA in the presence of the enzymic reducing agents than in the presence of NaBH4.

Neocarzinostatin-mediated DNA damage and repair in wild-type and repair-deficient Chinese hamster ovary cells.

The formation and repair of neocarzinostatin (NCS)-mediated DNA damage were examined in two strains of Chinese hamster ovary cells. The response in strain EM9, a mutant line selected for its sensitivity to ethyl methanesulfonate and shown to have a defect in the repair of X-ray-induced DNA breaks, was compared with that observed in the parental strain (AA8). The DNA strand breaks and their subsequent rejoining were measured using the method of elution of DNA from filters under either alkaline (for single-strand breaks), or nondenaturing conditions (for double-strand breaks).

Bleomycin-mediated DNA cross-links are dependent on closed-circular molecules with superhelical turns.

Non-covalent intermolecular DNA cross-links are created by reaction with the antitumor antibiotic, bleomycin. The cross-links are observed only when the reactant covalently closed circular duplex DNA contains either positive or negative superhelical turns. Multiple sites of cross-linking often extend over 500 base-pairs or more in length.