By Charles M. King (auth.), Lawrence J. Marnett (eds.)
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Hilbert 0, Romen W, Neumann H-G: The role of partial hepatectomy and promoters in the formation of tumors in non-target tissues of trans-4-acetylaminostilbene in rats. Carcinogenesis (4): 1519-1525, 1983. 51. Mulder GJ, Meerman JHN: Sulfation and glucuronidation as competing pathways in the metabolism of hydroxamic acids: The role of N,O-sulfonation in chemical carcinogenesis of aromatic amines. Environmental Health Perspectives (49): 27-32, 1983. 52. Dao TL: Studies on mechanism of carcinogenesis in th~ mammary gland.
ID u ID 0.. •• ::J ...... PG Biosynthesis •• •• • • ••• -. CD 50 Mutovenlclt, 10 Time 15 20 (min) FIGURE 7. Comparison of the time courses of PGH2 biosynthesis, BP-7,S-diol metabolism, and generation of a mutagen from BP-7,S-diol. Further support for epoxidation of BP-7,8-diol to the antidiolepoxide is the identification of RNA and DNA adducts formed as a result of incubation of BP-7,8-diol, PGH synthase, and polyguanylic acid or DNA (57,5S). Following digestion of the nucleic acid, the major guanosine and deoxyguanosine adducts were identified as arising by addition of the exocyclic amino group of guanosine to the benzylic carbon of the anti-diolepoxide (57,58).
Peroxyl radicals are moderately stable 55 eq. 1-10 sec) that are relatively selective oxidizing agents (67). They can abstract hydrogen to form hydroperoxides or insert oxygen into isolated double bonds. We have detected· and identified the hydroperoxide formed during peroxidatic metabolism of phenylbutazone and shown that it is reduced to an alcohol when incubated with microsomal preparations (P. H. Siedlik and L. J. Marnett, unpublished results). This accounts for the overall hydroxylation of phenylbutazone that occurs as a result of its oxidation by PGH synthase.
Arachidonic Acid Metabolism and Tumor Initiation by Charles M. King (auth.), Lawrence J. Marnett (eds.)