Nitroreduction of environmental nitrofluorenes by enzymes and rat mammary gland in vitro

Nitrofluorene (NF) compounds, widespread pollutants and potent mutagens, ar e tumorigenic for rat mammary gland suggesting a link to breast cancer. Red uction of nitrofluorenes, which may lead to their activation, was catalyzed by xanthine oxidase and ascorbate, catalysts of one electron nitroreductio n, 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, O-2 upta ke and amine formation, were enhanced by oxidation at C-9 (9-oxo-2,7-diNF> 2,7-diNF and 9-oxo-2NF> 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). Nitror eduction in vivo may lead to DNA adducts of the reduced nitrofluorenes and/ or DNA damage from the reactive oxygen species, and consequently, mammary g land tumorigenesis.