O6-Benzylguanine (BG) inactivates O6-alkylguanine-DNA alkyltransferase (AGT), resulting in an increase in the sensitivity of cells to the toxic effects of O6-alkylating agents. BG significantly enhances the cytotoxicity and decreases the mutagenicity of nitrogen mustards [i.e., phosphoramide mustard (PM), melphalan, and chlorambucil], a group of alkylating agents not known to produce O6-adducts...

Using a multidisciplinary approach, we have measured various indicators of DNA damage in peripheral lymphocytes of human populations potentially at increased risk for cancer. Sister chromatid exchanges (SCE) and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were evaluated in a group of firefighters; chromosomal aberrations and hprt mutations were evaluated in a group of cancer patients unde...

Following therapeutic administration, cyclophosphamide and Adriamycin are biotransformed to reactive metabolites, some of which are responsible for undesirable systemic toxicities of these chemicals, whereas others are responsible for their chemotherapeutic effectiveness. Microsomal mixed function oxidases activate cyclophosphamide to produce phosphoramide mustard and acrolein, while cytochrome...

Following therapeutic administration, cyclophosphamide and Adria mycin are biotransformed to reactive metabolites, some of which are responsible for undesirable systemic toxicities of these chemicals, whereas others are responsible for their chemotherapeutic effectiveness. Microsomal mixed function oxidases activate cyclophosphamide to pro duce phosphoramide mustard and acrolein, while cytochro...

A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, thiotepa, 1,3-bis(2-chloroe...

The DNA repair protein O-alkylguanine-DNA alkyltransferase (AGT) has been shown to protect cells from the toxic and mutagenic effect of alkylating agents by removing lesions from the O position of guanine. O-Benzylguanine (BG) is a potent inactivator of AGT, resulting in an increase in the sensitivity of cells to the toxic effects of chemotherapeutic alkylating agents. Chinese hamster ovary (CH...

BACKGROUND High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation is widely used in the treatment of several malignancies. The use of high-dose chemotherapy can be complicated by the occurrence of severe and sometimes life threatening toxicity. A wide interpatient variability in toxicity is encountered, which may be caused by variability in the pharmacokinet...

The bifunctional sulphur mustard (bis-(2-chloroethyl)sulphide, HD) and its monofunctional analogue (2-chloroethyl ethyl sulphide, CEES) are both vesicants. In this study, both mustards were shown to rapidly alkylate the AP2 consensus binding sequence incorporated in a 26mer oligonucleotide. The reaction was essentially complete within 10 min under the conditions employed in this study and -95% ...

The therapeutic effect of Cyclophosphamide (CPA) is thus attributed to phosphoramide mustard and acrolein leads the formation high levels reactive oxygen species (ROS), which results in decreased antioxidant activity. Excessive production ROS could also culminate oxidative stress. Objectives: This study aims evaluate sub-lethal dose cyclophosphamide, 5-FU, combination CPA on testicular status, ...

Hydrogenase, purified to an average specific activity of 328 mumol of H2 evolved/(min X mg of protein) from Clostridium pasteurianum W5, was found to have 4-5 Fe and 4-5 labile sulfur atoms per molecule of 60,000 molecular weight, in contrast with earlier reports of 12 Fe per molecule. Displacement of the iron-sulfur cluster from hydrogenase by thiophenol in 80% hexamethyl phosphoramide:20% H2O...