Bleomycins: new methods will allow reinvestigation of old issues.
The bleomycins (BLMs) are used clinically in combination chemotherapy, their clinical usefulness being limited by the accompanying pulmonary toxicity. Much has been learned about the structure and function of BLMs in vitro. However, the mechanism of their cytoxicity in vivo, including their target(s), metal cofactor(s) effecting nucleic acid cleavage and its (their) oxidation state, concentrations of BLM in the nucleus of the cell, BLM metabolism, hot spots for double-strand DNA cleavage, and their repair, have remained elusive. New methods offer new opportunities to revisit and solve old problems, which could ultimately lead to development of a more effective therapeutic.
Chen
Jingyang
J
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
Stubbe
JoAnne
J
D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000633:toxicity*; D001761:Bleomycin / Q000737:chemistry* / Q000633:toxicity*; D004249:DNA Damage; D019216:Metals, Heavy / Q000737:chemistry*; D015394:Molecular Structure
D000964:Antimetabolites, Antineoplastic; D019216:Metals, Heavy; D001761:Bleomycin