Nuclear Distribution of Aflatoxin B1 and Its Interaction with Histones in Rat Liver in Vivo

摘要: Abstract The distribution and retention of [3H]aflatoxin B1 (AFB1) residues in rat liver nuclear fractions were determined at 0.5, 2, 12, 36 hr following administration a single i.p. dose [3H]AFB1 (1 mg/kg body weight). Approximately 85 to 90% the nuclear-bound AFB1 was associated with chromatin 2 after aflatoxin treatment, remainder present nucleoplasmic fraction. Further fractionation showed that approximately 80% bound DNA, 10% removed by dialysis, remaining recoverable dialyzed protein apparent rate removal from DNA twice as fast (t1/2 = 12 hr) proteins (1/2 24 hr). Liver separated sodium dodecyl sulfate:polyacrylamide gel electrophoresis. No major differences observed Coomassie Blue dye-binding patterns control AFB1-treated animals for least postdosing. Although no significant radiolabeled peaks detected fraction, two peaks, accounting 50 60% total activity applied gel, each time point molecular weights 15,000 30,000. 5 these proteins, which identified histones their extraction 0.25 n HCI on polyacrylamide filtration columns acid:urea Specific measurements demonstrated histone H1 target residue binding an adduction level 3 4 times higher than any other histone. A linear, dose-dependent relationship H1, population noted over 16-fold range (0.125 2.0 mg per kg). Turnover rates function exposure labeling amino acids injection [14C]bicarbonate 22 prior treatment toxin sacrificing up days dosage protocol. half-life identical (approximately 3.5 days) both rats. However, either 0.125-or 1.0-mg/kg faster 1 day) decrease specific 14C-labeled backbone.