Activation of bleomycin-Fe(III) by bleomycin-Cu(II) and cysteine.
When bleomycin (BLM) was incubated with DNA at 37 degrees C for 30 minutes in the presence of BLM-Cu(II) and cysteine, the DNA became more acid-soluble compared with the reaction without BLM-Cu(II). Superoxide dismutase did not suppress this increased DNA chain breakage. This combination of BLM-Cu(II) and cysteine did not enhance BLM-Fe(II)-induced DNA chain breakage, but caused the DNA chain breakage by inactive BLM-Fe(III). Combination of BLM-Fe(III) with BLM-Cu(II) and cysteine also caused production of malondialdehyde-like product from DNA. Anaerobic incubation of DNA with BLM-Fe(III) and BLM-Cu(I) followed by aerobic incubation produced malondialdehyde-like product, but the incubation with CuCl instead of BLM-Cu(I) did not. These results suggest that activation of BLM-Fe(III) by BLM-Cu(II) and cysteine seems to be due to the reduction of BLM-Fe(III) to BLM-Fe(II) by BLM-Cu(I) formed in the reaction of BLM-Cu(II) and cysteine.
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology* / Q000031:analogs & derivatives; D003545:Cysteine / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000378:metabolism*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis; D051381:Rats
D004273:DNA, Neoplasm; C023502:copper bleomycin; C023503:iron bleomycin; D001761:Bleomycin; D008315:Malondialdehyde; D003545:Cysteine