Metabolism of N-Nitrosohexamethyleneimine To Give 1,6-Hexanediol Bound to Rat Liver Nucleic Acids23

Abstract

Rats were gavaged with the liver carcinogen N-nitrosohexamethyleneimine labeled with ³H or ¹⁴C and killed 16 hours later. The liver RNA and DNA were isolated and hydrolyzed with 1 M HCI at 100°C. Chromatography of the ³H-labeled RNA hydrolysate on a cation exchange resin (NH₄⁺ form), with water elution, separated five radioactive peaks, with peak “E” containing 27% of the bound ³H. There were no radioactive peaks in the 7-substituted guanine region. Hydrolysis of the ³H-labeled DNA gave a similar profile, but E contained only 5% of the ³H. The major component of E was identified as 1,6-hexanediol by its behavior and/or that of its benzoate derivative on cation exchange, anion exchange, thin-layer and gas-liquid chromatography, and by recrystallization of a mixture of the E and diol benzoates to constant specific radioactivity.