Genotoxicity of a Diesel Mutagen
Human Biomonitoring and Carcinogen Activation
Section:
Section of Molecular Carcinogenesis
Diesel exhaust is known to induce tumours in animals and is suspected of being carcinogenic in humans. Of the compounds found in diesel exhaust, 3-nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspected human carcinogen forming multiple DNA adducts in vitro and we are continuing to investigate the genotoxicity of this compound and its major metabolite 3-aminobenzanthrone (3-ABA). We have found that these compounds form DNA adducts, cause DNA strand breaks and induce micronucleus formation in human cells, demonstrating their genotoxicity in mammalian cells. 3-NBA also induced GC to TA base substitution mutations in the liver, colon and bladder of lambda/lacZ transgenic mice, while there was no increase in mutation frequency in lung, kidney, spleen and testis, broadly in accord with the extent of DNA adduct formation in the tissues, The metabolite 3-ABA was shown to be activated by human and rat liver microsomal fractions by a cytochrome p450-dependent pathway, principally involving P450 1A1 and 1A2. This metabolite may serve as suitable biomarker of human exposure to diesel exhaust and studies to investigate this are planned.
In the Section of Molecular Carcinogenesis
