We have strong evidence that N-hydroxy-2-acetylaminofluorene (N-OH-AAF) in mammary glands of female rats is activated via a lipoxygenase-peroxidase pathway. In this pathway, hydroperoxy fatty acids (HPETE) are formed by a lipoxygenase present in the targe tissue, mammary gland parenchymal cells. The HPETE then acts as a substrate for a peroxidase which in its reduction of HPETE to hydroxy fatty acids (HETE) oxidizes N-OH-AAF to the nitroxyl free radical form of the carcinogen which then dismutates to form 2-nitrosolfluorene (NOF) and N-acetoxy-2-acetylaminofluorene (n-OAc-AAF), the latter of which is a potent mammary gland carcinogen. The enzyme(s) glutathione peroxidase also acts as a substrate for HPETE and therefore the level of this enzyme, as controlled by the selenium status of the animal, will effect the amount of carcinogen that is activated. We plan to test the validity of the lipoxygenase-peroxidase model in isolated mammary cells from normal as well as from female rats receiving various treatments imposed to influence the control points in the putative model in a manner such as to effect the rate of N-OH-AAF metabolism. Various treatments which will be imposed on the animals include: A) alteration of selenium status, B) alteration of dietary antioxidant levels and C) alterations of dietary lipoxygenase inhibitor. The effect these treatments have on the rate of carcinogen metabolism as well as many other enzyme activities in the isolated cells will be determined. This study will test the lipoxygenase-peroxidase model of carcinogen activation in isolated mammary gland parenchymal cells.
| Floyd, Robert A (2009) Serendipitous findings while researching oxygen free radicals. Free Radic Biol Med 46:1004-13 |
| Floyd, R A; Henderson, R; Watson, J J et al. (1986) Use of salicylate with high pressure liquid chromatography and electrochemical detection (LCED) as a sensitive measure of hydroxyl free radicals in adriamycin treated rats. J Free Radic Biol Med 2:13-8 |
| Floyd, R A; Watson, J J; Wong, P K et al. (1986) Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation. Free Radic Res Commun 1:163-72 |
| Floyd, R A; Watson, J J; Harris, J et al. (1986) Formation of 8-hydroxydeoxyguanosine, hydroxyl free radical adduct of DNA in granulocytes exposed to the tumor promoter, tetradecanoylphorbolacetate. Biochem Biophys Res Commun 137:841-6 |
