Abstract
Nitrofluorene (NF) compounds, widespread pollutants and potent mutagens, are tumorigenic for rat mammary gland suggesting a link to breast cancer. Reduction of nitrofluorenes, which may lead to their activation, was catalyzed by xanthine oxidase and ascorbate, catalysts of one electron nitroreduction, by diaphorase, a catalyst of two electron nitroreduction, and by cytosol and microsomes of rat mammary gland. Regardless of the catalyst, the rates of reduction, monitored via reduction of acetylated cytochrome c, O2 uptake and amine formation, were enhanced by oxidation at C-9 (9-oxo-2,7-diNF>2,7-diNF and 9-oxo-2-NF> 9-OH-2-NF> 2-NF) and number of nitro groups (9-oxo-2,4,7-triNF>>9-oxo-2,7-diNF>9-oxo-2-NF and 2,7- and 2,5-diNF> 2-NF). Nitroreduction in vivo may lead to DNA adducts of the reduced nitrofluorenes and/or DNA damage from the reactive oxygen species, and consequently, mammary gland tumorigenesis.