The biological effects of N3-methyladenine.

The targeting of damage to DNA remains an attractive strategy to kill tumor cells. One of the serious side effects of alkylating agents is that they create both toxic (desired) and mutagenic (undesired) lesions. The result is that patients successfully treated for a primary cancer are at significant risk to develop cancer related to their therapy. To address this issue we have prepared agents that selectively methylate DNA at the N3-position of adenine. The presence of this lesion in DNA is thought to halt DNA polymerase, and this then initiates a cascade of events including cell death. The toxicity and mutagenicity of the compound, Me-lex, used to generate N3-methyladenine is discussed in bacterial, yeast, and mammalian systems. Mechanisms are proposed to explain the biological activities of N3-methyladenine. Copyright 2003 Wiley-Liss, Inc.