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By S. M. Fischer, T. J. Slaga (auth.), Susan M. Fischer, Thomas J. Slaga (eds.)

ISBN-10: 1461296315

ISBN-13: 9781461296317

ISBN-10: 1461326052

ISBN-13: 9781461326052

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Commun. ~:395, 1979. L. P. Ski n tumor-promoti ng activi ty of benzoyl peroxi de, a wi dely used free radical-generating compound. Science 213:1023-1025, 1981. 47 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. J. In: B. Sammuelsson, R. Paoletti, and P. ), Adv. Prostaglandin, Thromboxane and Leukotriene Research, Vol. 12, Raven Press, New York, 1983, pp. 309-312. M. J. Inhibition of tumor promotion by a biomimetic superoxide dismutase. Science 221: 75-77, 1983. W. A. Inhibition of oxygen radical metabolism in phorbol ester-activated poly morphonuclear leukocytes by an antitumor promoting copper complex with superoxide dismutase mimetic activity.

The effect of exogenously added PGs on arachidonic acid metabolism in this system is not known. Therefore. the next series of studies involved the use of inhibitors of various parts of the arachidonate cascade. Based on the role of PGs in inflammation. it was originally thought that the nonsteroidal anti-inflammatory agents. ie •• the cyclooxygenase inhibitors indomethacin or flurbiprofen. should inhibit promotion. In the SENCAR mouse. however. it was found that topical application of indomethacin can enhance TPA tumor promotion at doses of 25 to 100ug while inhibiting at higher.

Work by Slaga et al (45) showed that such free radical generating compounds as benzoyl peroxide, lauroyl peroxide and chloroperbenzoic acid have comp 1ete tumor promoti ng abil ity. Recentl y S1aga a nd coworkers (unpublished data) found that butylated hydroxyanisole and butylated hydroxytoluene are effective inhibitors of TPA and benzoyl peroxide promotion. The superoxide dismutase (SOD) mimetic Cu(II)(3,4-diisopropylsalicylic acid)2 (CuDIPS) has also been shown to inhibit both TPA promotion (47) and TPA-induced ODC (48).

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Arachidonic Acid Metabolism and Tumor Promotion by S. M. Fischer, T. J. Slaga (auth.), Susan M. Fischer, Thomas J. Slaga (eds.)

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