2-Acetamidofluorene and 3-Methylcholanthrene: Differences in Binding to Rat Liver Deoxyribonucleic Acid in vivo

Abstract

THE relationship between mutagenesis and carcinogenesis is still a matter of controversy¹. The problem is particularly unresolved with respect to liver cancer induced by chemicals. Although hepato-carcinogenic nitrosamines are known to alkylate liver DNA in vivo², similar binding to liver DNA in vivo has not been reported for the two other most intensively studied groups of liver carcinogens, namely, the fiuorenamines and the aminoazo dyes. Although, at present, one cannot make definitive interpretations of the functional significance (with respect either to DNA replication or to DNA transcription) of the binding of a carcinogen to the DNA in a liver cell, studies are needed which correlate carcinogenicity of various compounds with their binding in vivo to gene material. This report describes the binding of the strongly hepato-carcinogenic agent 2-acetamidofluorene³ (N-2-fluorenylacetamide, AAF) to rat liver DNA after intra-peritoneal injection. In a parallel in vivo experiment the aromatic hydrocarbon, 3 (or 20) -methylcholanthrene (MC), which is not carcinogenic for rat liver⁴ (although it does cause significant alterations in both RNA⁵ and protein⁶ synthesis in this organ), was found not to bind to rat liver DNA.