Indirect Alkylation of CBA Mouse Liver DNA and RNA by Hydrazine In Vivo. A Possible Mechanism of Action as a Carcinogen

Abstract

Treatment of inbred CBA mice with hydrazine sulfate. a liver carcinogen. plus [¹⁴C]formate or l-[methyl-¹⁴C]methionine as a source of “C₁” units, produced [¹⁴C]7-methylguanine (7-MG) in liver DNA and RNA. This methylated guanine was identified by its chromatographic characteristics in three different systems: on Sephadex G10, on Dowex 50, and by paper co-chromatography with authentic 7-MG. Mice that received [¹⁴C]formate alone showed no 7-MG in their DNA or RNA. In addition. mice treated with l-[methyl-¹⁴C]methionine alone showed no 7-MG in their DNA. These results suggest that “indirect” alkylation of nucleic acids is a mechanism of cancer initiation by hydrazine.