Secondary nitroalkanes: induction of DNA repair in rat hepatocytes, activation by aryl sulfotransferase and hepatocarcinogenicity of 2-nitrobutane and 3-nitropentane in male F344 rats.

The secondary nitroalkanes, 2-nitropropane, 2-nitrobutane, 3-nitropentane, 2-nitroheptane, nitrocyclopentane and nitrocyclohexane, as well as the primary nitroalkanes, 1-nitropropane, 1-nitrobutane, 1-nitropentane and 1-nitroheptane, were examined for their ability to induce DNA repair in rat hepatocytes and to serve as substrates for activation by partially purified rat liver aryl sulfotransferase in vitro. All of the secondary, but none of the primary nitroalkanes examined, induced significant DNA repair in rat hepatocytes. Also, the nitronates of all of the secondary nitroalkanes, but none of the primary nitroalkanes, served as substrates for the aryl sulfotransferase-catalysed production of 8-aminoguanosine and 8-oxoguanosine from guanosine in vitro. In a carcinogenicity assay using male F344 rats, the secondary nitroalkanes, 2-nitrobutane and 3-nitropentane, produced a highly significant incidence of hepatocarcinoma with metastases to the lungs, whereas the primary nitroalkane, 1-nitrobutane, was not carcinogenic. While a low incidence of hepatocarcinoma was also produced by cyclopentanone oxime, the results were not statistically significant. Since the secondary nitroalkane, 2-nitropropane, in contrast to the primary nitroalkane, 1-nitropropane, was also previously shown to be hepatocarcinogenic in rats, it is probable that secondary nitroalkanes constitute a hitherto unrecognized class of chemical carcinogens.