Activation of the liver carcinogen 2-nitropropane by aryl sulfotransferase
| Autor: | Guo Nie, Rama S. Sodum, Ock Soon Sohn, Emerich S. Fiala |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Pentachlorophenol Stereochemistry Nitroalkane Guanosine In Vitro Techniques Toxicology Nitroparaffins Nitrophenols chemistry.chemical_compound Propane Liver Neoplasms Experimental In vivo Animals Carcinogen Biotransformation Chromatography High Pressure Liquid chemistry.chemical_classification Aryl sulfotransferase General Medicine DNA Hydrogen-Ion Concentration Arylsulfotransferase Rats Inbred F344 Rats Enzyme chemistry Biochemistry Liver 2-Nitropropane Nucleic acid Carcinogens RNA |
| Zdroj: | Chemical research in toxicology. 7(3) |
| ISSN: | 0893-228X |
| Popis: | 8-Aminoguanine had previously been identified as one of the nucleic acid 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-O-sulfonate or acetate that would lead to NH2+, an aminating species, was proposed [Sodum et al. (1993) Chem. Res. Toxicol. 6, 269-276]. We now present in vivo and in vitro experimental evidence for the activation of 2-NP to an aminating species 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 modifications produced by 2-NP treatment. Furthermore, partially purified 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 species that aminated guanosine at the C8 position. This activation was dependent on the presence of the enzyme, its specific cofactor adenosine 3'-phosphate 5'-phosphosulfate, and mercaptoethanol. As in the case of the in vitro studies, pentachlorophenol and 2,6-dichloro-4-nitrophenol inhibited the in vitro formation of 8-aminoguanosine and 8-oxoguanosine. The corresponding primary nitroalkane, 1-nitropropane, which is not mutagenic and does not appear to be carcinogenic, was not a substrate for aryl sulfotransferase in the in vitro amination of guanosine. |
| Databáze: | OpenAIRE |
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