Administration of 1, 2-dimethylhydresine (DMH) produces colon cancer in rodents. Rats treated with DMH exhale ethane (Kang et al., 1968). These data suggest that methyl radicals (-CHs) are formed during the metabolism of DMH and they evolve as ethane, their dimeric form. The primary aim of this proposal is to explore how -CHs affects essential cellular components. To carry out the aim, experiments will be conducted in vivo as well as with model compounds under controlled conditions in vitro. The model compounds will include purified calf thymus DNA and a number of selected enzyme proteins, as well as their primary constituents, namely, deoxyribonucleotides and amino acids. The model compounds will be incubated in a system where -CHs (14 C-labeled) will be generated. How the structure of the model compounds are altered by -CHs will be determined by high performance liquid chromatography (HPLC) and gas chromatography/mass spectroscopy (GC/MS), and by nuclear magnetic resonance (NMR) as required. For the study of enzymes, functional modifications will also be determined by measuring enzymatic activities. Once the characteristics of the alterations are defined, the effects of DMH will be investigated in vivo. Rats will be treated with 14 C-DMH by i.p. injections. 14 C-Labeled macromolecules will be isolated from various rat organs, and then the structural modifications will be determined, using the in vitro studies as a guide. I believe that this work will produce valuable information concerning the mechanism of DMH- induced carcinogenesis and provide the groundwork for a long term project to establish conditions for protecting cells from alkyl radical-mediated damage.