Inhibition of bleomycin-induced [3H] thymidine 5'-triphosphate incorporation into liver and hepatoma nuclei by N-ethyl maleimide and daunomycin.

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Abstract
The addition of bleomycin to a nuclear incorporating system results in an increased incorporation of 3H-TTP into the DNA of rat liver and hepatoma nuclei. Bleomycin added to the nuclear incorporating system also produces scissions of DNA as determined by sucrose density gradient centrifugation of the extracted DNA. The action of bleomycin is dependent on the presence of sulfhydryl agents in the incubation mixture. Two compounds, N-ethylmaleimide and daunomycin, inhibit bleomycin induced incorporation of 3H-TTP preferentially. N-Ethylmaleimide inhibits bleomycin induced activity in liver and hepatoma 7777 nuclear equally. Lower levels of daunomycin inhibit bleomycin induced activity in hepatoma 7777 nuclei than are required to inhibit the activity in liver nuclei. The 2 compounds inhibit the bleomycin effect by different mechanisms. The addition of N-ethylmaleimide to bleomycin in the incubation system prevents bleomycin from causing breaks in DNA. The addition of daunomycin, despite inhibition of bleomycin induced 3H-TTP incorporation, does not affect competing with a sulfhydryl agent for bleomycin-sensitive sites on DNA. Daunomycin apparently inhibits a repair enzyme that is responsible for the increased incorporation following bleomycin treatment.