Alkylation of Purine Bases by Carbon-Centered Radicals
Mono- and di-substituted hydrazines are found ubiquitously (1, 2). They are present in the environment since they are used as herbicides, chemical intermediates, and as high energy fuels for rockets. They are found in plants such as tobacco and mushrooms. They are also present in medicine. All substituted hydrazines tested for carcinogenicity in long-term animal studies have been found to be positive (1). 1, 2-dimethylhydrazine (DMH) is a well known carcinogen that induces tumors specifically in the colon of rodents (3). Since DMH-induced lesions have characteristics that are remarkably similar to those of human colon cancer, this carcinogen is widely used as a model in the study of colon cancer. The ethyl derivative of DMH, 1, 2-diethylhydrazine (DEH), is also a carcinogen. DEH produces cancer in the thymus, liver, and brain (4). The mechanism(s) by which these di-alkyl hydrazines induce tumors is not known. Kang et al. (5) have shown that in rats the metabolism of DMH and DEH produces methyl radicals (·CH3) and ethyl radicals (·CH2CH3), respectively. Therefore, this investigation was conducted to explore the nature of the chemical interaction(s) between alkyl radicals and biomolecules using CH3 and RNA as models.
KeywordsAlkyl Radical Ethyl Radical Purine Base Chemical Intermediate Chemical Carcinogenesis
- 3.H. Druckrey. Organospecific carcinogenesis, in:“Topics in Chemical Carcinogenesis”, eds. W. Nakahara, S. Takayama, T. Sugimura, and S. Odashima, University Park Press, Baltimore, pp. 87 (1971).Google Scholar