Effect of L-Ascorbic Acid and DL-α-Tocopherol on the Activation and Binding of 2-Acetylaminofluorene to Rat Liver Nuclear Macromolecules in Vivo

Male Sprangue-Dawley rats which had been administered either ascorbic acid or DL-α-tocopherol for 4 weeks were injected intraperitoneally with a single dose of(9-¹⁴C)-2-acetylaminofluorens(AAF) 3.5hr before sacrifice. The activation and binding of a bepatocarcinogen. AAF to the nucleic acids and proteins rat liver nuclei were examined. After the precipitated DNA was enzymatically hydrolyzed and the adduct fraction was purified by Sephadex LH-20 chromatography, the individuals adduts were separated by HPLC. the liver microsomal and nuclear monooxygenase activities in AAF administered rats were increased, whereas those in ascobric acid and DL-α-tocopherol fed rats were decreased. It is suggested that microsomal and nuclear monooxygenase were essential for activated AAF to bind nucleic acid under the intracellular conditions. The inhibitory ability of ascobic acid and DL-α-tocopherol on the binding of AAF to liver nuclear DNA was most probably due to the marked inhibition of the formation of the proximate carcinogen. The protective effect of ascorbic acid and DL-α-tocopherol against the hepatocarcinogenic action of AAF may be mediated by decreased monooxygenase activities and by alteration in the binding of the esterified AAF to liver nucleic acids.