The novel chloroethylating agent 2-chloroethyl (methylsulfonyljmethanesulfonate (CIEtSoSo) has been shown to act like the Chloroethylnitrosoureas (CIEtNu's) in its DNA damaging and cytotoxic effects in human cell lines and has similar activity to the CIEtNu's in the National Cancer Institute antitumor screening tests. Its simpler chemistry, however, suggests that it may alkylate DNA more select...

Single doses of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea caused transient suppression of [3H]thymidine incorporation into DNA in bone marrow and gastrointestinal mucosa and more prolonged inhibition of such incorporation in B16 melanoma. A single dose of 1-(2-chloroethyl) -3- (trans-4-methylcyclohexyl) -1-nitro-sourea, 16 mg/kg, doubled the mean life-span after treatment of ...

The lethality for BALB/c mice of 1,3-bis(2-chloroethyl)-1-nitrosourea, cytosine arabinoside, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, hydroxyurea, mithramycin, a polymyxin-like antibiotic (SQ 21,286), polyadenylic polyuridylic acid, procarbazine, 5-[3,3-bis(2-chloroethyl)-1-triazeno]-imidazole-4-carboxamide (TIC-mustard) or uracil arabinoside administered in combination with Escherichia co...

Adult male Fischer rats were exposed to a necrogenic dose (200 mg/kg) of diethylnitrosamine or to nonnecrogenic doses of N-methyl-N-nitrosourea, 1,2-dimethylhydrazine, or benzo(a)pyrene following partial hepatectomy or sham hepatectomy. This treatment by itself led to no hepatocellular carcinomas by 8 to 18 months, except in animals given N-methyl-N-nitrosourea, which showed a 30% incidence by ...

The rate of rejoining of DNA strand breaks in L1210 cells exposed to X-irradiation has been studied using a recently developed technique for estimating DNA chain length: alkaline elution of prelabeled DNA through membrane fil ters. A marked inhibition of repair of single-strand breaks, has been produced by 2-chloroethyl isocyanate, a break down product in the decomposition of the antitumor agen...

A technique is described that greatly increases the efficiency of recovering specific locus point mutations in zebrafish (Danio rerio). Founder individuals that were mosaic for point mutations were produced by mutagenizing postmeiotic gametes with the alkylating agent N-ethyl-N-nitrosourea. Under optimal conditions, each founder carried an average of 10 mutations affecting genes required for em...

The presence of the DNA repair protein, 06-alkylguanine-DNA alkyltransferase (AGT) in tumor cells is a significant source of resistance to chemotherapeutic alkylnitrosoureas and alkyltriazenes. 06-Benzylguanine provides a means to effectively inactivate the AGT protein and increase the chemotherapeutic effectiveness of chloroethylating and methylating agents in vitro and in human tumor xenograf...

In a prospective, comparative evaluation of therapy in advanced gastrointestinal carcinoma with 5-fluorouracil, mitomycin C, and 1,3-bis-(2-chlorethyl)-l-nitrosourea used alone, in double combination, and in triple combination, 215 adults with proved gastrointestinal adenocarcinoma were randomly assigned to one of seven possible treatment programs. Dosages and schedules were determined from the...