Under the auspices of the Ministry of Health and Welfare of Japan and the Japanese Pharmaceutical Manufacturer Association, a collaborative study of the mouse lymphoma assay (MLA) was conducted by 42 Japanese laboratories and seven overseas laboratories to clarify the performance of the MLA for the detection of in vitro clastogens and spindle poisons. Twenty-one chemicals that were positive in ...

Observed only after administration of high doses, cardiotoxicity is the dose-limiting effect of cyclophosphamide (CY). We investigated the poorly understood cardiotoxic mechanisms of high-dose CY. A rat cardiac myocardial cell line, H9c2, was exposed to CY metabolized by S9 fraction of rat liver homogenate mixed with co-factors (CYS9). Cytotoxicity was then evaluated by 3-(4,5-dimethyl-2-thiazo...

The structures of boron-doped fullerene B-C59 (1) as a drug delivery system (DDS), two phosphoramides (2 and 3) which were analogous to the cyclophosphamide anticancer prodrug as well as their covalently bonded structures to B-C59 (4 and 5) were optimized by DFT computations at B3LYP level of theory using 6-31G(d) basis set. Comparing compounds 4 and 5 revealed that the chloro derivative (-1429...

that may arise as a result of combined therapy have not yet been fully researched and understood. This study examines the sensitivity of splenic and thymic lymphocytes to gluco corticoids and mitogens in vitro following in vivo treatment of animals with CY. CY is used in immunosuppression as well as cancer therapy (6). It has found application particu larly for acute and chronic lymphocytic leu...

Cyclophosphamide (CP) is metabolized to the reactive inter mediates, phosphoramide mustard (RAM) and acrolein (AC), which have generally different molecular binding targets. Sodium2-rnercaptoethanesulfonic acid (MESNA) has been used clinically to alleviate hemorrhagic cystitis caused by CP chemotherapy, has exhibited anticarcinogenic effects in rats exposed to CP during a long-term bioassay, an...

Cyclophosphamide (CPA), a widely used oxazaphosphorine anti-cancer prodrug, is inactive until it is metabolized by cytochrome P450 to yield phosphoramide mustard and acrolein, which alkylate DNA and proteins, respectively. Tumor cells transduced with the human cytochrome P450 gene CYP2B6 are greatly sensitized to CPA, however, the pathway of CPA-induced cell death is unknown. The present study ...

The importance of alkylating-agent dose intensity to cancer treatment is the subject of considerable comment. In recent years, this debate has often centered on the value of hematopoietic progenitor cell-supported high-dose alkylating agent regimens used in the treatment of hematopoietic cancers, Hodgkin’s disease, and breast cancer. Large randomized trials, lasting up to 10 years and requiring...

1. A quantitative study was made of the relationship between survival of colony-forming ability in Escherichia coli strains B/r and B(s-1) and the extents of alkylation of cellular DNA, RNA and protein after treatment with mono- or di-functional sulphur mustards, methyl methanesulphonate or iodoacetamide. 2. The mustards and methyl methanesulphonate react with nucleic acids in the cells, in the...

Previous NMR studies demonstrated that lonidamine (LND) selectively diminishes the intracellular pH (pHi) of DB-1 melanoma and mouse xenografts of a variety of other prevalent human cancers while decreasing their bioenergetic status (tumor βNTP/Pi ratio) and enhancing the activities of melphalan and doxorubicin in these cancer models. Since melphalan and doxorubicin are highly toxic agents, we ...