Triazenes: Synthesis and Chemical Properties.- Mechanisms of the Biological Actions of Triazenes.- Triazenes and Triazene N-Oxides: Antitumour Action in Animal Tumour Systems.- Antimestastatic Action of Triazene Derivatives.- Effects of Triazenes on Immune Responses.- Xenogenization of Experimental Tumors by Triazene Derivatives.- The Metabolism of Antineoplastic Triazenes.- Notes on the Metabolism, Pharmacokinetics and Mode of Action of N-Methyl and N-Ethyl-Triazenes in Relation to Their Pharmacological Activity.- Clinical Use of Triazenes.- Clinical Studies with the p-Carboxyl-Dimethyl-Phenyl-Triazene CB10-277.- Triazenes: Therapeutic Considerations and Perspectives.- Antitumor Imidazotetrazines: Prodrugs Targeted to the Major Groove of DNA.- O6-Alkylguanine-DNA-Alkyltransferase Gene Expression and the Cytotoxicity of Triazenes.- N-Methylmelamines, a Unique Class of Anti-Tumour Agents?.- Experimental Background and Early Clinical Studies with Imidazotetrazine Derivatives.- 'O6-Alkylguanine-DNA-Alkyltransferase: Significance, Methods of Measurement and Some Human Tumor and Normal Tissue Levels' (Contributions of the Workshop).- Summary of Poster-Sessions.- Contributors.

More than 25 years have elapsed since the development of the seminal idea which led to the synthesis of dimethyl triazenes as antitumor agents. The original suggestion of Shealy et ale was to use 4-imidazone-carboxarnide as the carrier of a nitro- gen-containing cytotoxic function. 5-diazoimidazole-4-carbox- amide (diazo-IC) was synthesized and tested in mice as a potential inhibitor of de novo purine biosynthesis. Its lack of antitumor action was attributed to its polarity and to the resulting poor uptake of this hydrophilic chemical. Diazo-IC was then coupled with dimethylamine, yielding 5, (3,3-dimethyl- l-triazeno)imidazole-4-carboxamide) (DTIC) with the intention of obtaining a less polar and more lipophil~c prod rug which might release diazo-IC intracellularly. Preliminary tests showed that DTIC had good antiumor activity in experimental systems. Further tests demonstrated a broad spectrum of action against rodent tumors, and clinical trials indicated activity against human malignancies. Subsequent clinical use of DTIC has demonstrated its usefulness against malignant melanoma, for which it is currently the drug of choice, and its effective- ness in combination chemotherapy in the treatment of other human cancers. Because of its antitumor activity the mechan- ism of action of DTIC has been investigated in some detail. The original rationale for its development, that is, the hydrolysis in vivo to diazo-IC, has been shown not to be in- volved in th-e-mechansims of action. DTIC requires metabolic acti- vation before it exerts its biological effects.

Cape May Point, New Jersey, is home to a natural phenomenon of stunning proportions. Each autumn millions of migrating birds converge here on their annual flight to wintering grounds as far away as Brazil and Peru. Season at the Point, the rich and telling story of the birds and birders of Cape May, evokes the sense of mystery and excitement that pervades the Cape as birders gather to count owls by the hundreds, hawks by the tens of thousands, and shorebirds and songbirds by the hundreds of thousands.

3156The National Institute for Occupational Safety and Health (NIOSH) received a confidential employee request for a health hazard evaluation from a veterinary teaching hospital in Michigan. Employees were concerned about reproductive problems and hair loss that they associated with work-related exposures to chemotherapy drugs. NIOSH's findings and recommendations are discussed.