Metabolism of the oesophageal carcinogen N-nitrosomethylamylamine: changes with age, clearance from blood and DNA alkylation

Abstract

Freshly excised rat oesophagus and other tissues metabolize N-nitrosomethyl-n-amylamine (NMAA) to 2-, 3-, 4- and 5-hydroxy-NMAA (HO-NMAA), and 3- and 4-oxo-NMAA. We examined the development of this metabolism in MRC-Wistar rats and Syrian hamsters. In rats, oesophagus showed maximum metabolism at nine days of age, and forestomach showed considerable metabolism at three days, but none in adults. In newborn hamsters, oesophagus showed 10.4%; and in three-day hamsters, forestomach showed 4.9% metabolism, despite low or no metabolism by the adult tissues. Clearance of NMAA (25 mg/kg) from rat blood had a half-life of 21 min. The blood also contained considerable amounts of 4-oxo- and 4-HO-NMAA. Incubation of adult oesophagus and liver slices with 3H-labelled NMAA produced DNA labelling, including labelled N7-and O6-methylguanine, with 14 times higher specific radioactivity in DNA from oesophagus than from liver. O6-Methylguanine was also measured by radioimmunoassay.