Adriamycin oxygen

The release of iron from intracellular ferritin stores is thought to involve the reduction of Fe to Fe " (Funk et al., 1985) and one would expect this reduction to be fecilitated by the low oxygen tension, increased levels of reducing species and the low pH shown by nuclear magnetic resonance (NM to be as low as 6.9 after only 6 h of cold storage (Fuller et al., 1988). Exogenous redox-active quinones such as adriamycin have been shown to catalyse lipid peroxidation in the presence of ferritin under hypoxic conditions (Vile and Winterbourne, 1988), and lipid peroxidation is stimulated in micro-somes in the presence of purified ferritin and flavin... 

Komiyama, T., Kikuchi, T., and Sugiura, Y., 1986, Interactions of anticancer quinone dmgs, aclacinomycin A, adriamycin, carbazilquinone, and mitomycin C, with NADPH-cytochrome P-450 reductase, xanthine oxidase and oxygen, J. Pharmacobiodyru 9 651-664. 

Figure 5-23 Stereoscopic drawing showing a molecule of daunomycin (Fig. 5-22) intercalated between two base pairs in a molecule of double-helical DNA, d(CGTACG). Nitrogen and oxygen atoms are shown as dots. From Quigley et al.220 Both daunomycin and adriamycin (doxorubicin 14-hydroxy-daunomycin) are important but seriously toxic anticancer drugs.

Berlin, V. and Haseltine, W.A. (1981) Reduction of adriamycin to a semiquinone-free radical by NADPH cytochrome P-450 reductase produces DNA cleavage in a reaction mediated by molecular oxygen, J. Biol. Chem. 256, 4747-4756. 

Sinha, B.K. et al. (1989) Adriamycin activation and oxygen free radical formation in human breast tumor cells protective role of glutathione peroxidase in adriamycin resistance, Cancer Res. 49, 3844-3848. 

It has been shown that the renal bioactivation of xenobiotics such as the herbicides paraquat and diquat [10, 111, 112], and of p-lactams such as cephaloridine and cefsulodin [10, 40, 41] or the antitumor agent adriamycin [113, 114] can induce the generation of reactive oxygen species (oxidative stress) which can be involved in alterations of the structure and functions of cell membranes, cytoskeletal injury, mutagenicity, carcinogenicity, and cell necrosis [115-117]. 

Gianni L, Zweier JL, Levy A, Mayers CE. Characterisation ofthe cycle of iron-mediated electron transfer from adriamycin to molecular oxygen. J Biol Chem 1985 260(11) 6820-6826. 

There is complete reduction of a p- or o-quinone to the corresponding hydroquinone or catechol, respectively. In the human liver, carbonyl reductase may play a role in the reduction of some quinones. Catechols are primary substrates for catechol o-me-thyl transferase, but also undergo sulfation. However, for the antitumor quinones, mitomycin C, adriamycin, and daunomycin, two-electron reduction serves as an efficient bioactivation mechanism, elegantly affirming the concept of bioreductive alkylation for the preferential bioactivation of antitumor prodrugs with oxygen deficient tumors. 

Alegria, A.E. and Riesz, P. (1988) Photochemistry of aqueous adriamycin and daunomycin. A spin trapping study with 170 enriched oxygen and water, Photochem. Photobiol., 48, 147-152. 

E. Oxygen may potentiate toxicity via enhanced generation of tree radicals with some chemotherapeutic agents (eg, bleomycin, adriamycin, and daunoru-bicin). 

Kim, D.S., Kim, H.R., Woo, E.R., Hong, S.T., Chae, H.J., and Chae, S.W. 2005. Inhibitory effects of rosmarinic acid on adriamycin-induced apoptosis in H9c2 cardiac muscle cells by inhibiting reactive oxygen species and the activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase. Biochemical pharmacology, 70,1066-1078. 

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