Search results for "Phosphoramide Mustards"
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Induction of DNA breaks and apoptosis in crosslink-hypersensitive V79 cells by the cytostatic drug beta-D-glucosyl-ifosfamide mustard.
2001
To study molecular aspects of cytotoxicity of the anticancer drug β-D-glucose-ifosfamide mustard we investigated the potential of the agent to induce apoptosis and DNA breakage. Since β-D-glucose-ifosfamide mustard generates DNA interstrand crosslinks, we used as an in vitro model system a pair of isogenic Chinese hamster V79 cells differing in their sensitivity to crosslinking agents. CL-V5B cells are dramatically more sensitive (30-fold based on D10 values) to the cytotoxic effects of β-D-glucose-ifosfamide mustard as compared to parental V79B cells. After 48 h of pulse-treatment with the agent, sensitive cells but not the resistant parental line undergo apoptosis and necrosis, with apopt…
Observations on the effects of cyclophosphamide, phosphoramide mustard and some activated oxazaphosphorines on murine L1210 leukemia.
1984
The L1210 tumor system was used in vitro and in vivo in comparative studies with activated cyclophosphamide analogs, cyclophosphamide and phosphoramide mustard. All the above compounds gave substantial cell kills (5 logs) of L1210 in vivo at doses that were non-toxic, but slight differences were noted. ASTA Z 7557 had a slight advantage in cure rate over cyclophosphamide when these drugs were given i.v. or i.p. to early tumor (i.p.). However, cyclophosphamide had the advantage in cure rate when drug administration was i.v. to advanced tumor. At equimolar concentrations in vitro ASTA Z 7557 was more cytotoxic than either phosphoramide mustard or acrolein. In vivo, the activated cyclophospham…
Induction of DNA crosslinks and DNA strand lesions by cyclophosphamide after activation by cytochrome P450 2B1
1997
Cyclophosphamide requires metabolic activation by cytochrome P450 to exert its genotoxic effects. Therefore in vitro studies on its mechanism of action have been limited to the use of self-activating derivatives of cyclophosphamide or to hepatocytes as an activating system. In this study we used a cell line of Chinese hamster lung fibroblasts (V79 cells), genetically engineered to express active cytochrome P450 2B1 as the sole observable cytochrome P450 (SD1 cells). An increase in DNA strand lesions (SL: DNA single-strand breaks and alkali labile sites) was observed between 0.5 and 1.5 mM cyclophosphamide (24 h incubation) which could be classified as alkali labile sites using a modified al…