The toxic effects of the combinations of amphotericin B (AmB) and actinomycin D or AmB and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea were measured against the human promyelocytic leukemia cells HL-60. The toxicities of both drug combinations were greater than the additive toxicity of each of the drugs used singly, but the exact conditions under which synergism was achieved differed for each ...

The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea on the rejoining of X-ray-induced DNA strand breaks were examined in normal human fibroblasts (WI-38) and a simian virus 40-transformed derivative (VA-13) with the use of alkaline sucrose sedimentation. 1,3-Bis(2-chloroethyl)-1nitrosourea was capable of partially inhibiting repair of Xray-produced DNA strand breaks in both cell types when the ...

A previous study using a single injection of (chloro-2-ethyl)ribofuranosyl-3-nitrosourea has indicated the low acute hematotoxicity of this nitrosourea. However, because the hematotoxicity of nitrosourea is usually cumulative, we have studied the effect of injecting (chloro-2-ethyl)ribofuranosyl-3-nitrosourea (15 mg/kg) dissolved in 0.2 ml sterile oil C57BL X i.p. into DBA/2F1 mice for 5 consec...

Upon ethyl nitrosourea treatment of RNA of tobacco mosaic virus, up to four phosphodiester groups may be alkylated per molecule without chain breakage, as shown be sucrose gradient centrifugation. This indicates that ribophosphotriesters are quite stable. However, when this alkylation reaction is of longer duration and 6 to 10 triesters are formed, then an average of 1 to 2 breaks occurs and li...

The relationship between cell cycle position and cytotoxicity was studied in 9L rat brain tumor cells treated with nitrosoureas that, de pending on their structures, can alkylate or alleviate and cross-link DNA and/or carbamoylate biomolecules. Because pure populations of Gì-, S-, and Gz-M-phase cells could not be obtained with the centrifugal elutriation methods used, drug sensitivity of cell...

Measurements of the response of the EMT6 mouse tumor to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea by either tumor volume or the in vitro assay of the cell surviving fraction give very different results. For BCNU very little delay in tumor growth is caused by high doses of the drug, whereas the surviving fraction assayed 2 hr after dru...

Mouse blastocysts were exposed in vitro to various concentrations of N-methyl-N-nitrosourea and 3-methylcholanthrene. The incorporation of [3H]thymidine, [3H]uridine, and [3H]leucine into the exposed blastocysts was determined either immediately following exposure or after 18 hr of culture. The concentrations of N-methyl-N-nitrosourea or 3-methylcholanthrene used had no effect on blastocyst via...

The lethal effects of two nitrosourea derivatives, 1,3-bis(2-chloroethyl)-1-nitrosourea and 4-[3-(2-chloroethyl)-3-nitrosoureido]-cis-cyclohexanecarboxylic acid, on a continuous line of human colon carcinoma cells (LoVo cells) were investigated. The survival response of exponentially growing and stationary-phase LoVo cells to both drugs were of the threshold exponential type. Survival was ident...

Drug resistance in myeloid leukemias may be mediated by an increased capacity to repair chemotherapy-induced DNA damage. Some tumor cell lines that are resistant to nitrosoureas contain the DNA repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase). This protects cells by removing cytotoxic, nitrosourea-induced O6-alkylguanine adducts. We measured the level of alkyltransferase a...

The relationship between cell cycle position and cytotoxicity was studied in 9L rat brain tumor cells treated with nitrosoureas that, depending on their structures, can alkylate or alkylate and cross-link DNA and/or carbamoylate biomolecules. Because pure populations of G1-, S-, and G2-M-phase cells could not be obtained with the centrifugal elutriation methods used, drug sensitivity of cells i...