Carcinogenesis, Vol. 20, No. 10, 2017-2023,
October 1999
© 1999 Oxford University Press
Carcinogenesis |
Potent carcinogenicity of 2,7-dinitrofluorene, an environmental pollutant, for the mammary gland of female Sprague–Dawley rats
1 Veterans Affairs Medical Center, Minneapolis, MN 55417 and
2 Department of Laboratory Medicine and Pathology, University of Minnesota Medical School and
3 University of Minnesota Comprehensive Cancer Center, Minneapolis, MN 55455, USA
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.
Abbreviations: 2-AAF, 2-acetylaminofluorene; 2-AF, 2-aminofluorene; CIS, carcinomain situ; DMSO, dimethyl sulfoxide; 2,5-diNF, 2,5-dinitrofluorene; 2,7-diNF, 2,7-dinitrofluorene; 2-NF, 2-nitrofluorene; nitro-PAHs, nitrated polycyclic aromatic hydrocarbons; PAHs, polycyclic aromatic hydrocarbons; SD, Sprague–Dawley; 2,4,7-triNF, 2,4,7-trinitrofluorene.
4 To whom correspondence should be addressed at: VA Medical Center, 1 Veterans Drive (151), Minneapolis, MN 55417, USAEmail: malej001{at}maroon.tc.umn.edu