Isotope effect on the carcinogenicity of 3-methylcholanthrene in mouse skin by selective deuteration of the 1-methylene group: biological evidence for a mechanism of tumor initiation.
3-Methylcholanthrene (MC) in chloroform and trifluoroacetic acid-d1 yielded 3-methylcholanthrene-d4 (MC-d4), a compound selectively deuterated at the 1-, 5-, and 6-carbon atoms. In turn, the protodedeuteration of the labeled hydrocarbon at the 6-carbon atom led to 3-methylcholanthrene-d3 (MC-d3). A comparative test for carcinogenicity between MC and MC-d3 by repeated skin painting on female Swiss mice showed a significantly lower tumorigenic activity of the latter. The result implies that the 1-carbon atom of the hydrocarbon is a critical binding-site to cellular targets in the tumor-initiating process.
D000818:Animals; D003903:Deuterium; D005260:Female; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008748:Methylcholanthrene; D051379:Mice; D008968:Molecular Conformation; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship; D014269:Trifluoroacetic Acid
D008748:Methylcholanthrene; D003903:Deuterium; D014269:Trifluoroacetic Acid