Electron spin resonance study on the metabolism of 2-naphthylamine and 1-naphthylamine in rat liver microsomes.

Incubation of 2-naphthylamine (2-NA) with rat liver microsomes fortified with NADPH resulted in the formation of two types of free radicals which were identified as being due to N-hydroxy-2-naphthylamine and 2-amino-1-naphthol. The former radical was shown to be oxidized further to 2-nitrosonaphthalene radical. Compared with the case of the constitutive microsomes, the amount of the free radicals increased progressively on using the microsomes from methylcholanthrene (MC)-induced or phenobarbital (PB)-induced rats. On the other hand, the amount of the free radical formed from 1-naphthylamine (1-NA) was much less than that from 2-NA, so that the radical structure was not identified unambiguously. The enzymes involved in this case were not induced by either MC or PB. Thus, from the viewpoint of free radical formation, the metabolic patterns of 2-NA and 1-NA are quite different and such different behavior might be correlated with the distinct difference in their carcinogenicities. From the inhibitory effects of carbon monoxide, SKF-525A, alpha-naphthoflavone and 1-(1-naphthyl)-2-thiourea on the free radical formation, it was concluded that both mixed function oxidases (cytochrome P-450s) and mixed function amine oxidase (dimethylaniline monooxygenase) are involved in the metabolism of 2-NA.