METABOLISM OF 2-ACETYLAMINOFLUORENE BY RAINBOW-TROUT

In order to examine factors that may contribute to the reported resist ance of rainbow trout, Shasta strain, to the well-known hepatocarcinog enic effects of 2-acetylaminofluorene (AAF), the in-vitro and in-vive metabolism of [C-14]AAF in trout has been examined. Trout (compared to rat) liver microsomes metabolized AAF more efficiently, producing 3-f old larger amounts of ring-hydroxylated metabolites (7-hydroxy-AAF and 5-hydroxy-AAF), but 5-fold less N-hydroxy-AAF. Freshly isolated trout hepatocytes extensively metabolized AAF to form the same ring-hydroxy lated metabolites and their respective glucuronide and sulfate conjuga tes. N-OH-AAF (plus its conjugates) and covalently-bound AAF derivativ es amounted, respectively, to <1% and 1.4-1.6% of total metabolites. L iver DNA of trout treated with AAF contained a single AAF-DNA adduct i dentified as N-(deoxyguanosin-8-yl)-2-aminofluorene (the major persist ent AAF-DNA adduct found in rat liver). The level of this adduct (12 a ttomoles/mu g DNA) was about 1000-fold lower than the level of AAF-DNA adduct previously reported in rat liver. The data show that trout liv er, compared to rat liver, is considerably less efficient in metaboliz ing AAF to carcinogenic metabolites, and more efficient in forming non toxic products, thus possibly explaining, in part, the resistance of t rout to AAF-induced hepatocarcinogenesis.