Streoptozotocin, Chlorozotocin and Related Nitrosourea Antitumour Agents
In 1959, 1 -methyl-1 -nitroso-3-nitroguanidine (MNNG) was found to increase the life span of mice bearing leukaemia L1210 ( 1). While MNNG did not have sufficient activity to warrant extensive clinical testing, the demonstration of antitumour effect gave impetus for further evaluation of the N-nitroso class of compounds as potential antineoplastic agents. In 1961 1-methyl-1-nitrosourea (MNU) was reported to be not only more effective against intraperitoneally implanted L1210 than MNNG, but also was capable of penetrating the blood-brain barrier; MNU produced limited but reproducible antitumour activity in mice with intracerebral leukaemic cells ( 1). Since that time over 300 aIkyInitrosourea compounds have been screened for antitumour activity, the majority of the synthetic work having been undertaken by Montgomery, Johnston and co-workers at the Southern Research Institute (3).
KeywordsWhite Blood Cell Count Antitumour Activity Pyridine Nucleotide Bone Marrow Toxicity L1210 Leukaemia
Unable to display preview. Download preview PDF.
- 2.Skipper, H.E., Schabel, F.M., Jr., and Wilcox, W.S. (1964). Experimental evaluation of potential anticancer agents. XII. On the criteria and kinetics associated with “curability” of experimental leukemia. Canc. Chemotherapy Rep., 35, 1–111.Google Scholar
- 3.Carter, S.K. (1973). An overview of the status of the nitrosoureas in other tumors. Cancer Chemotherapy Rep., 4, 35–46.Google Scholar
- 4.Walker, M.D. (1973). Nitrosoureas in central nervous system tumors. Cancer Chemotherapy Rep., 4, 21–26.Google Scholar
- 5.Moertel, C.G. (1973). Therapy of advanced gastrointestinal cancer with the nitrosoureas. Cancer Chemotherapy Rep., 4, 27–34.Google Scholar
- 17.Cowens, W., Brundratt, R. and Colvin, M. (1975). Mechanism of action of bischloroethyl nitrosourea. Proc. Am. Assoc. Cancer Res., 66, 100.Google Scholar
- 19.Schein, P.S., Bull, J., McMenamin, M.G. and Macdonald, J.S. ( 1975). DNA synthesis by human bone after incubation with BCNU or chlorozotocin (DCNU, NSC-178248). Proc. Am. Assoc. Cancer Res., 66, 122.Google Scholar