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PubMed2005

Analysis of chemical warfare agents. II. Use of thiols and statistical experimental design for the trace level determination of vesicant compounds in air samples.

Thermal desorption with gas chromatography-mass spectrometry (TD-GC-MS) remains the technique of choice for analysis of trace concentrations of analytes in air samples. This paper describes the development and application of a method for analysing the vesicant compounds sulfur mustard and Lewisites I-III. 3,4-Dimercaptotoluene and butanethiol were used to spike sorbent tubes and vesicant vapours sampled; Lewisite I and II reacted with the thiols while sulfur mustard and Lewisite III did not. Statistical experimental design was used to optimise thermal desorption parameters and the optimum method used to determine vesicant compounds in headspace samples taken from a decontamination trial. 3,4-Dimercaptotoluene reacted with Lewisites I and II to give a common derivative with a limit of detection (LOD) of 260 microg m(-3), while the butanethiol gave distinct derivatives with limits of detection around 30 microg m(-3).

Arsenicals↗
PubMed1950

The effect of podophyllotoxin, colchicine, urethane, and nitrogen mustard on the respiration of normal and suprarenalectomized rat lymphatic tissue.

The injection of podophyllotoxin, colchicine, and a nitrogen mustard derivative, methyl-bis(beta-chloroethyl)amine, into normal animals causes a reduction of the respiration of the lymphatic tissues, spleen, and/or thymus. No effect was demonstrable on kidney, a representative tissue of non-lymphatic origin. The degree of inhibition was considerably less in suprarenalectomized animals, suggesting that the inhibition is mediated by the suprarenal gland.

Animals↗
PubMed1977

Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test.

Seventeen cancer chemotherapeutic agents were tested for their ability to mutate Salmonella typhimurium tester strains in the Salmonella/microsome mutagenicity test. There was a high correlation between the mutagenicity and carcinogenicity of a given agent. Carcinogens positive in the test were Adriamycin, daunomycin, 1-propanol-3,3'-iminodimethanesulfonate, cyclophosphamide, isophosphamide, hycanthone, chlornaphazin, nitrogen mustard, uracil mustard, melphalan, and thio-tepa. Two carcinogesn, actinomycin D and bleomycin, were not detected as mutagens. The presumptive noncarcinogen, methotrexate, was negative in the test. Tilorone and 6-mercaptopurine, tentatively classified as noncarcinogens, were mutagenic. The carcinogenicity of cis-dichlorodiammineplatinum(II), which was positive in the test, has not been determined.

2-Naphthylamine↗
PubMed1983

Cytocidal action of the quinone group and its relationship to antitumor activity.

Many clinically useful antitumor agents have a quinone group in their structure. A series of model compounds has been studied to determine if the quinone group is involved in the cytotoxic activity of these agents and to investigate the mechanism of this action. Hydrolyzed benzoquinone mustard, which contains a quinone group, produced significant cell kill of L5178Y lymphoblasts, whereas hydrolyzed aniline mustard, which has a similar chemical structure but contains no active functional groups, showed little activity against this cell line. Benzoquinone mustard, which possesses both a quinone moiety and an active alkylating group, was approximately 30,000 times more active against L5178Y cells than was hydrolyzed benzoquinone mustard. It was approximately 600 times more active than aniline mustard, a compound which has the same alkylating group but no quinone function, and 200 times more active than an equimolar combination of aniline mustard and hydrolyzed benzoquinone mustard. The cytotoxic activity of hydrolyzed benzoquinone mustard was inhibited by either superoxide dismutase or catalase, while catalase but not superoxide dismutase inhibited the activity of benzoquinone mustard. Neither enzyme had any effect on the cytocidal action of aniline mustard. These studies suggest that the presence of a quinone group in the chemical structure of a compound can result in significant cell kill by a mechanism that appears to involve free radicals and active oxygen species. In addition, if the compound contains an alkylating group which can bind to DNA, as well as a quinone moiety, the cytocidal activity of the agent appears to be enhanced and is greater than that resulting from an additive effect of the two groups.

Animals↗