During the past 90 years, hydrazine compounds have been studied in animal cells grown in the laboratory, in live animals, and in humans. More than 400 hydrazine analogs (related compounds) have been screened for their ability to kill tumors. In 1996, a retrospective review of scientific studies in which the anticancer activity of hydrazine analogs was investigated found that 65 of 82 evaluated compounds showed some anticancer activity in xenograft models (tumor cells of one species transplanted to another species). Of the 82 tested compounds, seven showed activity against human tumor cells and were, therefore, selected for further testing in pilot studies and phase I clinical trials. Among these seven compounds, only procarbazine (a methylhydrazine derivative, also called ibenzmethyzin or natulan) completed preliminary testing in humans. Procarbazine exhibited anticancer activity in patients with Hodgkin disease, melanoma, and lungcarcinoma, and it was ultimately used in several first-line treatment regimens in the 1960s.[1,2,3] In view of the initial success with procarbazine, hydrazine sulfate, which is similar in chemical composition, was investigated for anticancer activity beginning in the 1970s. During this period, investigation of hydrazine sulfate as a treatment for cancer-related cachexia was also initiated. Research on hydrazine sulfate both as a single agent and in combination with standard chemotherapy regimens continued through the mid-1990s.[4,5,6,7,8,9]
Although it was proposed in the early 1900s that hydrazine compounds are toxic to animals and to humans, they have been administered as antidepressant (e.g., iproniazid), chemotherapy (e.g., procarbazine), and antituberculosis (e.g., isoniazid) drugs. In addition to medicinal uses, hydrazine compounds have been used in industry and agriculture as components of rocket fuel, as herbicides, and as antioxidants in boiler and cooling-tower water.[10,11,12] Many scientists consider hydrazine sulfate and other hydrazine analogs to be cancer-causing agents, and they have expressed concern about the safety of these compounds.[1,10,12,13,14,15,16,17,18,19,20,21] In the 10th Report on Carcinogens, hydrazine and hydrazine sulfate are listed by the U.S. Department of Health and Human Services' National Toxicology Program as "reasonably anticipated to be human carcinogens." When the antituberculosis drug isoniazid and hydrazine antidepressants are combined with purified DNA in the laboratory, they produce hydrogen peroxide and free radicals that can damage the DNA.[14,17,23] Hydrazine compounds have been reported to cause mutations and chromosome damage in bacteria and in plant and animal cells.
Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.
Creating evidence-based summaries on cancer genetics is challenging because the rapid evolution of new information often results in evidence that is incomplete or of limited quality. In addition, established methods for evaluating the quality of the evidence are available for some, but not all, aspects of...