Tumorigenicity and genotoxicity of an environmental pollutant 2,7-dinitrofluorene after systemic administration at a low dose level to female rats.

Abstract

Environmental pollution with nitroaromatic compounds may pose health hazards. We have examined the tumorigenicity in female Sprague-Dawley rats of 2,7-dinitrofluorene (2,7-diNF) and 9-oxo-2,7-diNF administered by intraperitoneal (i.p.) and oral routes at 10 micromol/kg body weight, 3 times per week for 4 weeks. After i.p. treatment, the estimated median latency for the combined malignant and benign mammary tumors was decreased in 2,7-diNF- (p = 0.003) or 9-oxo-2,7-diNF-treated (p = 0.007), relative to vehicle-treated rats (42 or 64 vs. 80 weeks, respectively), whereas after oral dosing, there were no significant differences. At 90 weeks, the malignant mammary tumor incidence in 2,7-diNF-, 9-oxo-2,7-diNF- and vehicle-i.p. treated rats was 44 (p = 0.02 vs. vehicle-treated), 25 and 6%, respectively. Liver and mammary gland DNA was analyzed by HPLC combined with electrospray tandem mass spectrometry for the presence of a deoxyguanosine (dG-2,7-diNF) adduct and a deoxyadenosine (dA-2,7-diNF) adduct derived from 2,7-diNF, and a deoxyguanosine (dG-9-oxo-2,7-diNF) adduct derived from 9-oxo-2,7-diNF. Both dG-2,7-diNF and dA-2,7-diNF were detected in DNA of 2,7-diNF-treated rats, whereas only very low levels of dG-9-oxo-2,7-diNF were detected in DNA of 9-oxo-2,7-diNF-treated rats. After i.p. treatment, the dA-2,7-diNF level was higher (p < 0.01) in the mammary gland than liver (13.6 vs. 7.8 adducts/10(8) nucleotides). In the mammary gland, the dG-2,7-diNF level was higher (p < 0.05) after i.p. than oral dosing and also higher (p < 0.05) than in the liver (36 vs. 8.6 and vs. 9.1 adducts/10(8) nucleotides, respectively). The preferential display of carcinogenicity and genotoxicity in the mammary gland by low doses of 2,7-diNF signifies its potential relevance for environmental breast cancer.

• Authors: Danuta Malejka-Giganti, Daniel R Parkin, Richard W Decker, Gloria A Niehans, Robin L Bliss, Mona I Churchwell, Frederick A Beland
• Journal: International journal of cancer (Int J Cancer) Vol. 122 Issue 9 Pg. 1958-65 (May 01 2008) ISSN: 1097-0215 [Electronic] United States
• PMID: 18183586 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• 2-nitroso-7-nitro-9-oxofluorene
• 2-nitroso-7-nitrofluorene
• Carcinogens, Environmental
• DNA Adducts
• Environmental Pollutants
• Fluorenes
• Mutagens
• Nitroso Compounds
• 2,7-dinitrofluorene
• Deoxyguanosine
• Ascorbic Acid

Topics

• Administration, Oral
• Animals
• Ascorbic Acid (pharmacology)
• Carcinogens, Environmental (metabolism, toxicity)
• Chromatography, High Pressure Liquid
• DNA Adducts (drug effects, metabolism)
• Deoxyguanosine (metabolism)
• Environmental Pollutants (administration & dosage, metabolism, toxicity)
• Female
• Fluorenes (administration & dosage, metabolism, toxicity)
• Incidence
• Injections, Intraperitoneal
• Kaplan-Meier Estimate
• Liver Neoplasms, Experimental (chemically induced, metabolism)
• Mammary Neoplasms, Experimental (chemically induced, metabolism)
• Mutagens (metabolism, toxicity)
• Nitroso Compounds (toxicity)
• Rats
• Rats, Sprague-Dawley
• Tandem Mass Spectrometry