A series of experiments evaluated the antileukemic effect of an agent which elevates cellular cyclic adenosine 3':5'-monophosphate levels by phosphate levels by inhibiting phosphodiesterase. When administered alone, theophylline had only modest antileukemic effects, but it had synergistic effects when administered with 1,3-bis(2-chloroethyl)-1-nitrosourea. This synergism produced an improved th...

The effect of combining chemotherapy and immunostimulation, induced by a chemical, against a murine lymphoid leukemia was investigated. When tetramisole or levamisole were used following one administration of 1,3-bis(2-chloroethyl)-l-nitrosourea, a significantly higher percentage of long-term surviviors occurred in contrast to the groups of animals treated with drug or immunostimulant alone. Th...

Different biological aspects of a novel 2-chloroethyl nitrosourea derived from cysteamine, N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]-N'- nitrosourea (CMSOEN2), were studied. Drug-induced cytotoxic effects, uptake kinetics, DNA damage, and O6-alkylguanine-DNA alkyltransferase activity were determined in 3 melanoma cell lines: the murine B16 and 2 human metastatic-derived cell lines (M4 Beu ...

N-Ethyl-N-nitrosourea-induced transplacental renal carcinogenesis in the rat results primarily in Wilms' tumors, apparently because primitive nephroblasts are the preferred target. Our question is whether N-ethyl-N-nitrosourea-induced mutations in the fetal kidney would increase the number of adult-type renal cell carcinomas in the Eker rat, which is heterozygous for a mutation that predisposes...

Interference of oncogenic N-nitrosourea in intraocular tumor induction by human adenovirus type 12 in rats was examined. Transplacental administration of methylnitrosourea to rat embryo reduced significantly the latent period of the intraocular adenovirus tumor in each animal whereas in groups preadministered with ethylnitrosourea the decrease in the latent period showed marked individual varia...

The effectiveness of heat therapy in combination with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea on a murine ependymoblastoma was investigated. Based on survival time and the number of survivors, whole-body hyperthermia (40 degrees) increased the therapeutic effectiveness of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Heat alone did not modify the course of the tumor. Microscopic evidence o...

Five permanent tumor cell lines derived originally from either a solid or an ascites biopsy of rat hepatoma exhibited differential sensitivities to bleomycin, Adriamycin, 1-beta-D-arabinofuranosylcytosine, hydroxyurea, 1-trans-(2)-chloroethyl)-3-(4-methoylcyclohexyl)-1-nitrosourea, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. The cells were least sensitive to hydroxyurea and 1-beta-D-arabi...

The effectiveness of heat therapy in combination with i -(2chboroethyl)-3-cycbohexyl-1-nitrosourea on a murine ependy mobbastomawas investigated. Based on survival time and the number of survivors, whole-body hyperthermia (40°)increased the therapeutic effectiveness of 1-(2-chboroethyb)-3-cycbohexyl 1-nitrosourea. Heat alone did not modify the course of the tumor. Microscopic evidence of accel...

Although the antitumor effects of chloroethylnitrosoureas have been shown to be due primarily to DNA-DNA cross-linking by the alkylating moieties of these agents, the basis of the often accompanying bone marrow toxicity has been more controver sial. We report on the relative bone marrow toxicity of four model nitrosoureas with different alkylating and Carbamoylating activi ties: 1,3-bis(2-chlor...