DNA topoisomerases are enzymes responsible for the relaxation of DNA torsional strain, as well as for the untangling of DNA duplexes after replication, and are important cancer drug targets. One class of topoisomerase inhibitors, "poisons", binds to the transient enzyme-DNA complex which occurs during the mechanism of action, and inhibits the religation of DNA. This ultimately leads to the accu...

General pharmacology in -the seventeenth and eighteenth centuries is considered (Parts 1 and 2). Reference is made to some criticisms of the contemporary materia medica and -to early attempts at a scientific investigation of drugs and poisons. The studies of vegetable drugs by Stoerk and Withering are discussed to illustrate the problems associated with pharmaco-dynamic studies in clinical prac...

At the beginning of the twentieth century it was common to administer poisons to get rid of unwanted people, or simply to ingest poisons by accident. The science of forensic toxicology was not well developed yet, and many death certificates were issued without properly identifying the cause of death. Pulitzer Prize–winning science writer Deborah Blum has created a larger story structured like a...

The two known antineoplastic quinoxaline topoisomerase II poisons, XK469 (NSC 697887) and CQS (chloroquinoxaline sulfonamide, NSC 339004), were compared for DNA cleavage site specificity, using purified human topoisomerase IIalpha and human topoisomerase IIbeta. The DNA cleavage intensity pattern for topoisomerase IIalpha poisoning by CQS closely resembled that of VM-26, despite the lack of any...

Topoisomerase II (TOP2)-targeting poisons such as anthracyclines and etoposide are commonly used for cancer chemotherapy and kill tumor cells by causing accumulation of DNA double-strand breaks (DSB). Several lines of evidence indicate that overexpression of TOP2A, the gene encoding topoisomerase IIα, increases sensitivity of tumor cells to TOP2 poisons, but it is not clear why some TOP2A-overe...

You’re late for work, and it’s pouring rain. In the parking lot, a car speeds around you and takes the last spot near the building entrance. You end up trudging from the back of the lot and get soaked to the skin. You’re mad, and you know your judgment at the moment is probably impaired. Worse, the leftover anger will continue to color your decisions at work, our research suggests, without your...