Activation of 2-acetylaminofluorene in the nuclei of rat liver.

2-Acetylaminofluonana, a potent hapatocarcinogan, bound to DNA when incubated with an isolated nuclei from mat liven. Nuclear monooxygenase was essential for this binding as shown by dependence on reduced nicotinamide adenina dinucleotide phosphate. The binding was in creased by pretreatment of rats with 3-methylcholanthrane and was completely inhibited by the preincubation of nuclei with the antibody against reduced nicotinamida adanine d inucleotida phosphate-cytochmome c neductase. Addition of microsomes to nuclei from untreated rats increased the binding of 2-acetylaminofluorene to DNA. Addition of mi crosomas from 3-methylcholanthrene-tmeated mats had about 5 times more effect on binding than had microsomes from untreated rats. The increase of this binding was inhibited by preincubation of microsomes with the anti body, indicating that microsome-activated 2-acetylamino fluorene entered into the nuclei. On the other hand, the addition of microsomes to the nuclei from 3-mathylcholan threna-treatad rats decreased the binding of 2-acatybami nofluorana to DNA. The addition of the microsomas from untreatedratsresultedin a greaterdecreasein binding than d id microsomas from 3-methylcholanthrane-treated rats. These phenomena could be explained by the change in the influx and afflux of 2-acatylaminofluonana activated in nuclei and microsomas across nuclear membrane. The present study suggests that intracellular activation of 2acetylaminofluorana occurs not only in the andoplasmic reticulum but also in the nuclear envelope.