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Physical Binding of Labeled 20-Methylcholanthrene to Mouse Epidermal Subcellular Fractions¹

Pacific Northwest Research Foundation, Seattle, Washington 98104

When applied to mouse skin, ³H-labeled 20-methylcholanthrene (MC) is physically absorbed by the chromatin, mitochondria, microsomes, and cytosol of mouse epidermis. Label remained associated with cytosol protein after removal of free MC and any low-molecular-weight metabolites by dialysis, gel filtration, and ultrafiltration; this association reached a maximum around 3 hr after application of MC to mouse skin. Although previous work reported covalent binding to mouse skin cytosol, most of the material bound to cytosol protein after mild isolation of cytosol and removal of low-molecular-weight radioactivity is easily removed by precipitation of the protein with ethanol or trichloroacetic acid. Enzymatic digestion established that most of the MC loosely bound to the cytosol or chromatin was in fact bound to protein. Electrophoresis of the MC-bound cytosol protein on 7% basic polyacrylamide gels showed that most of the activity was associated with a protein fraction that had the same mobility as bovine or mouse serum albumin. The binding to the cytosol fraction and to chromatin was inhibited by the simultaneous application of 7,12-dimethylbenz(a)anthracene or the promoter 12-O-tetradecanoyl-phorbol-13-acetate, and was less inhibited by benz(a)anthracene or the nonpromoter phorbol-13,20-diacetate. We suggest that the binding to the cytosol receptor protein and to chromatin may be involved in the promoting stage of mouse skin tumorigenesis.

¹ This work was supported in part by Grant CA-13155-01 from the National Cancer Institute of the NIH.

Received 8/24/72. Accepted 2/12/73.