Arachidonic acid-dependent metabolism of (±)-7,8-dihydroxy-7,8-dihydrobenzo[A]pyrene to polyguanylic acid-binding derivatives

Panthananickal, A.; Marnett, Lawrence J.

doi:10.1016/0009-2797(81)90044-2

Cited by 33 publications

(10 citation statements)

References 27 publications

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Section: Stereochemistry Of Peroxyl Radical-dependent Epoxidation Of mentioning

confidence: 99%

“…The stereoselectivity of epoxidation of BP-7,8-diol by peroxyl radicals is distinct from that exhibited by cytochromes P-450 (36). Oxygen introduction by peroxyl radicals occurs on the same side of the molecule as the 8-hydroxyl group, whereas oxygen introduction by cytochromes P-450 is determined primarily by the orientation of the pyrene moiety with respect to the active site of the enzyme (36,37). Confirmation of the importance of the 8-hydroxyl group to the stereochemistry of epoxidation by peroxyl radicals is provided by the observation that 7,8-dihydrobenzo[a]pyrene is epoxidized to both enantiomers of 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene to equal extents (38).…”

Section: Stereochemistry Of Peroxyl Radical-dependent Epoxidation Of mentioning

confidence: 99%

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Peroxyl free radicals: potential mediators of tumor initiation and promotion

1987

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In recent years, there has been an explosion of interest in the involvement of free radicals in carcinogenesis (1-4). This seems a natural outgrowth of the long overdue realization that free radicals are formed in biological systems and that they contribute significantly to physiological and pathological processes. Much of the emphasis of research linking free radicals and cancer has focused on intermediates of oxygen reduction such as superoxide anion and hydroxyl radical (2). There is another family of oxygencentered free radicals that have received less attention but may be just as important biologically as reduced oxygen intermediates. This Commentary is intended to familiarize the reader with some of the properties of peroxyl radicals and to explain how these species participate in reactions that are relevant to tumor initiation and promotion. Experimental data are presented that are intended to be provocative rather than definitive because this area of investigation is just beginning to evolve.

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Section: Stereochemistry Of Peroxyl Radical-dependent Epoxidation Of mentioning

confidence: 99%

Section: Stereochemistry Of Peroxyl Radical-dependent Epoxidation Of mentioning

confidence: 99%

Peroxyl free radicals: potential mediators of tumor initiation and promotion

1987

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“…6-Hydroxybenzo[a]pyrene is further oxidized either spontaneously or metabolically to the 1,6-, 3,6-, or 6,12-quinones. This phenol is also a presumed intermediate in the oxidation of benzo [a]pyrene to the three quinones catalyzed by prostaglandin endoperoxide synthetase (Panthanickal and Marnett 1981). Evidence exists for the further oxidative metabolism to two additional phenols.…”

Section: Health Effectsmentioning

confidence: 99%

The Gulf Oil Spill

2011

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“…The (-)-enantiomer of BP-7,8-diol is epoxidized to the (+ )-enantiomer of the antidihydrodiolepoxide by both peroxyl radicals and cytochromes P450. In contrast, the (+ )-enantiomer of BP-7,8-diol is epoxidized to the (-)-enantiomer of the antidihydrodiolepoxide by peroxyl radicals, but to the (+ )-enantiomer of the syn-dihydrodiolepoxide by cytochromes P450 (84). Dihydrodiolepoxides hydrolyze to tetrahydrotetraols that are readily separable by HPLC, which enables one to quantitate the amounts of the dihydrodiolepoxides produced and to identify the oxidant responsible for their formation (85).…”

Section: Techniques For Quantitating Hydroperoxide-dependent Oxidationsmentioning

confidence: 99%

“…Stereochemistry has been used to differentiate epoxidation of polycycic hydrocarbon dihydrodiols by peroxyl radicals and cytochromes P450 (84). Figure 3 summarizes the stereochemical considerations that make this approach feasible.…”

Section: Techniques For Quantitating Hydroperoxide-dependent Oxidationsmentioning

confidence: 99%

Prostaglandin synthase-mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates.

Marnett

1990

Environ Health Perspect

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Prostaglandin-H synthase is unique among enzymes of the plant and animal kingdom in its ability to biosynthesize and metabolize hydroperoxides. Its cyclooxygenase activity oxygenates polyunsaturated fatty acids to hydroperoxy endoperoxides, and its peroxidase activity reduces the hydroperoxy group to hydroxy groups. Higher oxidation states of the peroxidase oxidize reducing substrates to electron-deficient derivatives that react with macromolecular nucleophiles. In the case of aromatic amines, the electrondeficient derivatives are mutagenic to bacterial and mammalian cells. 3-Dicarbonyl compounds and retinoic acid are oxidized to carbon-centered radicals that react with 02 to form peroxyl free radicals. Peroxyl radicals are the most stable oxy radicals and are able to diffuse some distance from the site of their generation. Peroxyl radicals are also formed during lipid peroxidation and in the reaction of polyunsaturated fatty acid hydroperoxides with metal complexes and metalloproteins. Peroxyl radicals epoxidize isolated doubled bonds of compounds such as 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene ; 3,4-dihydroxy-3,4-dihydrobenzo(a)anthracene; and aflatoxin B1. The epoxide products represent the ultimate carcinogenic forms of the respective compounds. Techniques for quantitating the extent of peroxidase dependent or peroxyl radical-dependent metabolism in vivo make use of differences in the structure or stereochemnistry of reactive intermediates formed by peroxidases relative to cytochromes P450. Differences in the relative amounts of hydrolysis products and DNA adducts derived from anti-and syn-dihydrodiolepoxides following application of BP-7,8-diol to mouse skin in vivo indicate peroxyl radicals play a significant role in metabolism of BP-7,8-diol in uninduced animals.

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Arachidonic acid-dependent metabolism of (±)-7,8-dihydroxy-7,8-dihydrobenzo[A]pyrene to polyguanylic acid-binding derivatives

Cited by 33 publications

References 27 publications

Peroxyl free radicals: potential mediators of tumor initiation and promotion

Peroxyl free radicals: potential mediators of tumor initiation and promotion

The Gulf Oil Spill

Prostaglandin synthase-mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates.

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