ACTIVATION OF THE LIVER CARCINOGEN 2-NITROPROPANE BY ARYL SULFOTRANSFERASE

8-Aminoguanine had previously been identified as one of the nucleic ac id base modifications produced in livers of rats by treatment with the hepatocarcinogen 2-nitropropane (2-NP), and a hypothetical mechanism of activation of 2-NP to hydroxylamine-0-sulfonate or acetate that wou ld lead to NH2+, an aminating species, was proposed [Sodum et al. (199 3) Chem. Res. Toxicol. 6, 269-276]. We now present in vivo and in vitr o experimental evidence for the activation of 2-NP to an aminating spe cies by rat liver aryl sulfotransferase. Pretreatment of rats with the aryl sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4- nitrophenol significantly decreased the levels of liver nucleic acid m odifications produced by 2-NP treatment. Furthermore, partially purifi ed rat liver aryl sulfotransferase was shown to activate 2-NP and 2-NP nitronate in vitro at neutral pH and 37 degrees C, to a reactive spec ies that aminated guanosine at the C8 position, This activation was de pendent on the presence of the enzyme, its specific cofactor adenosine 3'-phosphate 5'-phosphosulfate, and mercaptoethanol. As in the case o f the in vivo studies, pentachlorophenol and 2,6-dichloro-4-nitropheno l inhibited the in vitro formation of 8-aminoguanosine and 8-oxoguanos ine. The corresponding primary nitroalkane, 1-nitropropane, which is n ot mutagenic and does not appear to be carcinogenic, was not a substra te for aryl sulfotransferase in the in vitro amination of guanosine.