Enhancement of chemotherapy agents

Enhancement of the DNA cross-linking activity of melphalan by misonidazole in vivo

“…When administered 30 min prior to MEL (5mgkg-1), DEM (700mgkg-1) caused a pronounced enhancement of cross-linking in both spleen and tumour at 6 h post-injection (Table III). Millar, 1982, andMcNally, 1982). As mentioned earlier, the mechanism of this chemosensitization effect is still very unclear, although there is general agreement that the tumour response is somewhat more pronounced than that of normal tissues.…”

In vitro potentiation of BCNU activity in rat brain tumour cells pretreated with misonidazole

“…Anti-tumour agents whose activities are most effectively enhanced both in vitro and in vivo by sensitizers include cyclophosphamide, melphalan and the nitrosoureas (for review see Millar, 1982;McNally, 1982;Siemann, 1982Siemann, , 1984. In vitro experiments of chemopotentiation have concentrated primarily on exposing cells to the sensitizer in the absence of oxygen (usually for a period of 2-4h) prior to treatment with the chemotherapeutic agent in air.…”

“…Several antitumour drugs have been investigated extensively in this manner; particularly the alkylating agent melphalan (Stratford et al, 1980;Roizin-Towle & Hall, 1981;Taylor et al, 1982). In vitro combinations of nitrosoureas and MISO, especially those evaluating the hypoxic cell pre-incubation effects, have been far more limited (Twentyman, 1980(Twentyman, , 1982 despite the large enhancement ratios which can be obtained when MISO is added to in vivo therapies incorporating some of the compounds in this anti-tumour agent class (McNally, 1982;Siemann, 1982Siemann, , 1984.…”

Enhancement of the action of alkylating agents by single high, or chronic low doses of misonidazole

“…The electron-affinic radiosensitizer misonidazole (MISO) has been shown to be a potent enhancer of the actions of certain chemotherapeutic drugs in mouse tumours (for review see McNally (1982)). In general, nitrogen mustards and certain nitrosoureas appear to be the drugs with which MISO is most effective.…”