EARLY FORMATION OF DNA-ADDUCTS COMPARED WITH TUMOR-FORMATION IN A LONG-TERM TUMOR STUDY IN RATS AFTER ADMINISTRATION OF 2-NITROFLUORENE

2-Nitrofluorene (NF) is a model compound for nitroarenes which has bee n identified in diesel exhaust and in urban air. The current study was carried out to observe the carcinogenicity of different doses of NF t o 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 contro l, whereas the other three groups of rats were fed basal diet suppleme nted 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 we re 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 hig h 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 hepat ocellular carcinomas, 16 had forestomach squamous carcinomas and 15 ha d 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 administrat ion were dose- and time-dependent. Ten days after the start of NF admi nistration DNA adduct levels were found to be 54, 11 and 6 DNA adducts /10(8) normal nucleotides in forestomach, liver and kidney respectivel y. In the non-tumor target organs levels in the range 1.7-4.8 DNA addu cts/10(8) normal nucleotides were found. DNA adduct formation in this study showed a good correlation with the localization of tumors, altho ugh there is a need for additional factors for tumor formation. The re sults indicate that DNA adduct formation is an important factor for tu mor formation and suggest that DNA adducts could be used as biomarkers for genotoxic risk.