Cancer nitrosoureas

Boileau, T. W., Z. Liao, S. Kim et al. 2003. Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. J Natl Cancer Inst 95(21) 1578—1586. 

Among the most active alkylating agents used against cancer are nitrosoureas and aziridines. 

Lomustine (CCNU) -nitrosourea alkylating agent cell cycle independent -bone marrow suppression (delayed, prolonged, and cumulative) -nausea and vomiting -pulmonary fibrosis Lung Cancer... 

Aliosman, F., Caughlan, J., and Gray, G.S. (1989) Diseased DNA intrastrand cross-linking and cytotoxicity induced in human brain tumor cells by 1,3-fcis(2-chlorocthyl)-1 -nitrosourea after in vitro reaction with glutathione. Cancer Res. 49, 5954. 

Carbamate esters of zinc, zineb, and ziram are carcinogenic and teratogenic in animals, but this is attributed to the action of the carbamate esters and not to zinc (Elinder 1986). Results of studies with small mammals showed zinc to be cocarcinogenic with 4-nitroquinoline-N-oxide on oral cancer, and with N-ethyl-N-nitrosourea on brain cancer (Leonard and Gerber 1989). 

Although N-methyl-N-nitrosourea can induce cancer in human beings, its derivatives were found to be potent antitumor agents. l,3-Bis(2-chloroethyl)-l-nitrosourea (BCNU), l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and l-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-l-nitrosourea (PCNU) l-(2-Choroethyl)-3-(4-methylcyclo-hexyl)-l-nitrosourea and l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea showed antitumor activity by alkylating with DNA [82-84]. N-Nitrosourea-based prodrugs designed to become activated by tumor-associated proteases were found to provide enhanced... 

Alkylating agents were the first drugs to be used to treat highly proliferating cancers. They are mainly of two types the relatively non-specific nitrogen mustards and the even less selective nitrosoureas. 

RoscOE, J.P. and Claisse, P.J. (1978). Analysis of N-ethyl-N-nitrosourea induced brain carcinogenesis by sequential culturing during the latent pe iod. I. Morphology and tumorigenicity of the cultured ceUs and their growth in agar, J. NatL Cancer Inst. 61,381. 

Yamaguchi, T., Nakagawa, M., Hidaka, K., Yoshida, T., Sasaki, T., Akiyama, S. I., and Kuwano, M. (1985). Potentiation by squalene of anti-tumor effect of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-l-(2-chloroethyl)-nitrosourea in a murine tumor system. Jpn.. Cancer Res. 76, 1021-1026. 

Rickard, S.E., Yuan, Y.V., Chen, J., and Thompson, L.U. 1999. Dose effects of flaxseed and its lignan on N-methyl-N-nitrosourea-induced mammary tumorigenesis in rats. Nutr. Cancer 35, 50-57. 

Therapeutic applications Because of their ability to penetrate into the CNS, the nitrosoureas are primarily employed in the treatment of brain tumors. They find limited use in the treatment of other cancers. 

Wakui A. [Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas.] Gan To Kagaku Ryoho 1982 9(8) 1327-38. 

OiiveroVT, Toxicology and pharmacology of the nitrosoureas. Cancer Chemother rep. 4[3] 13-20,1973... 

Wheeler GP, A review of studies on the mechanism of action of tne nitrosoureas, in [Sartorelli AC ed.] Cancer Chemotherapy, volume 30, Washingtoon, DC American Chemical Society.pp87-119,1976... 

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