2-Nitrofluorene (NF) is a model compound for nitroarenes which has been identified in
diesel exhaust and in urban air. The current study was carried out to observe the carcinogenicity of different doses of NF to rats and
DNA adduct formation in different organs at an early stage of NF administration. One group of rats was fed basal diet as a control, whereas the other three groups of rats were fed basal diet supplemented with different amounts of NF (0.24, 0.95 and 2.37 mmol NF/kg diet, referred to as low, medium and high dose, respectively). The rats were exposed to NF continuously for 11 months, after which all groups of rats were fed basal diet without NF for another 13 months. In the high dose group
hepatocellular carcinomas were found in all rats (20/20), forestomach
squamous carcinomas in 11 and cortical kidney
carcinomas in 10 rats. Fifteen out of 19 rats fed the medium dose of NF had
hepatocellular carcinomas, 16 had forestomach
squamous carcinomas and 15 had cortical kidney
carcinomas. The major
tumors of the rats fed the low dose of NF were forestomach
squamous carcinomas (10/18).
DNA adducts formed in
tumor target organs after 1, 2, 6 and 10 days NF administration were dose- and time-dependent. Ten days after the start of NF administration
DNA adduct levels were found to be 54, 11 and 6
DNA adducts/10(8) normal
nucleotides in forestomach, liver and kidney respectively. In the non-
tumor target organs levels in the range 1.7-4.8
DNA adducts/10(8) normal
nucleotides were found.
DNA adduct formation in this study showed a good correlation with the localization of
tumors, although there is a need for additional factors for
tumor formation. The results indicate that
DNA adduct formation is an important factor for
tumor formation and suggest that
DNA adducts could be used as
biomarkers for genotoxic risk.