Potent carcinogenicity of 2,7-dinitrofluorene, an environmental pollutant, for the mammary gland of female Sprague-Dawley rats

Abstract

Nitrofluorene compounds are environmental pollutants chiefly from incomplete combustion. This study examined carcinogenicities after one intramammary injection of 2-nitrofluorene (2-NF), 2,7-dinitrofluorene (2,7-diNF) or dimethyl sulfoxide (DMSO) (solvent control) to 30-day-old and of 2-NF, 9-OH-2-NF, 9-oxo-2-NF, 2,7-diNF, 9-oxo-2,7-diNF, 2,5-dinitrofluorene, 9-oxo-2,4,7-trinitrofluorene, N-OH-2-acetylaminofluorene (N-OH-2-AAF) (carcinogen control) or DMSO to 50-day-old female Sprague-Dawley rats. In 30- and 50-day-old rats 6 and 8 glands/rat, respectively, were injected with 2.04 μmol of compound in 50 μl/gland of DMSO. Whereas all compounds including DMSO yielded combined malignant and benign mammary tumor incidences of 33-87% by week 82 after injection, 2,7-diNF produced 100 and 93% incidences significantly (P < 0.001) sooner than did DMSO, i.e. by weeks 23-49 and 18-48 after treatment of 30- and 50-day-old rats, respectively. Rats treated with 2,7-diNF and 9-oxo-2,7-diNF had significantly (P < 0.0001) and marginally (P = 0.0536) more mammary tumors, respectively, than DMSO-treated rats. In 2,7-diNF-treated rats, the ratio of malignant to benign mammary tumors was 5.4, whereas in all other groups it was < 0.5, N-OH-2-AAF, a potent tumorigen when applied to the mammary gland as a solid or in suspension, did not yield the expected tumorigenicity here. The contrasting tumorigenic potencies of 2,7-diNF and N-OH-2-AAF may have been prompted by differences in their solubilities in DMSO. Thus, the poorly soluble 2,7-diNF was slowly absorbed from the injection sites since residues (up to 0.9% of the dose injected) were recovered even after 45 weeks. The data indicate prolonged exposure of the mammary gland to 2,7-diNF and suggest that contamination of the environment with 2,7-diNF, even at low levels, poses substantial carcinogenic risk.