Butylated hydroxyanisole-stimulated NADPH oxidase activity in rat liver microsomal fractions.

Cummings, Scott W.; Prough, Russell A.

doi:10.1016/s0021-9258(17)44176-7

Cited by 63 publications

(16 citation statements)

References 11 publications

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“…It is possible that further ring hydroxylation is the preferred initial step in the metabolic pathw ay of 4-HA, with the subsequent possibilities of conjugation or oxidation to a quinone. Cummings & Prough (1983) have shown that the structurally related compound, BHA (E320) inhibits the mixed-function oxidase system through the formation of a quinone metabolite which diverts electrons from the microsomal electron-transport chain to the reduction of oxygen. In collaboration with other laboratories we are investigating modifications to 4-HA with the aim of improving its pharmacokinetic characteristics, by reducing hepatic metabolism without diminishing the tyrosinase affinity of the compound or its ease of oxidation by the enzyme.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Radicals and melanomas

Riley

1985

Phil. Trans. R. Soc. Lond. B

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The synthesis of melanin involves the oxidation of phenolic substrates by the enzyme tyrosinase. In vertebrates tyrosinase is present only in specialized cells (melanocytes), where it catalyses the oxidation of tyrosine and certain diphenolic intermediate products to quinones which polymerize to give rise to melanin. This specialized metabolic pathway provides a possible approach to the specific chemotherapy of malignant tumours of pigment cells (malignant melanoma). Certain analogues of tyrosine are oxidized by tyrosinase generating reactive orthoquinones with cytotoxic potential. One such analogue, 4-hydroxyanisole, has been investigated as a possible specific melanocytotoxic precursor. The parent compound inhibits DNA synthesis but exhibits little general toxicity, while the tyrosinase oxidation products are highly toxic to cells. The mechanism of this toxicity may involve semiquinone radicals. Encouraging initial results have been obtained from clinical pilot studies using intra-arterial infusion of hydroxyanisole in patients with localized recurrences of malignant melanoma.

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Section: Pharmacokineticsmentioning

confidence: 99%

Radicals and melanomas

Riley

1985

Phil. Trans. R. Soc. Lond. B

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“…This suggests that arachidonic acid itself or metabolites formed as a result of BHA treatment might also be involved in the process of BHA-induced carcinogenesis through enhanced production of oxygen radicals. In addition, BHA is a stimulator of the formation of reactive oxygen species (93,136,(138)(139)(140)(141)143). We therefore hypothesize that products of prostaglandin H synthase-mediated metabolism, in particular the production of prostaglandin E2, might be involved in the mechanism of BHA-induced enhancement of cell proliferation, as is shown in Figure 1-4.…”

Section: Effect Of Other Chemicals On Bha-induced Hyperplasiamentioning

confidence: 90%

“…In the chromosome aberration test, BHA appeared to be clastogenic to Chinese hamster ovary cells in the presence of a standard S9 mix or washed microsomes (93). The involvement of reactive oxygen species in the clastogenic effect of BHA was suggested by Cummings (1983) (136) and Rössing (1985) (138) who demonstrated that BHA increased the formation of hydrogen peroxide by microsomes. Oxidative demethylation of BHA by cytochrome p450 followed by the stepwise oneelectron oxidation of TBHQ into its semiquinone radical and its corresponding quinone.…”

Section: Prooxidant Activity Of Bhamentioning

confidence: 97%

“…These metabolites of oxidative metabolism have been found in »' « pi'fro systems. TBHQ, TBQ and BHA-OH are major metabolites of BHA in liver microsomes (98,135,136). Both 2-BHA and 3-BHA are easily metabolized to di-BHA by purified rat intestine peroxidase and horse radish peroxidase (137) and by rat liver microsomes (99,135).…”

Section: Tissue Distribution and Excretion Of Bhamentioning

confidence: 99%

“…Hydrogen peroxide is then formed by dismutation of superoxide and the quinone may again be reduced (136). The clastogenic effect of BHA in the presence of microsomes can therefore be ascribed to the quinone-metabolites of BHA which attack DNA via the formation of reactive oxygen species (93).…”

Section: Prooxidant Activity Of Bhamentioning

confidence: 99%

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BHA and cancer risk : the role of prostaglandin H synthase in the carcinogenicity of butylated hydroxyanisole

Schilderman¹

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Butylhydroxyanisol (BHA) [MAK Value Documentation in German language, 1986]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 11. Lieferung, Ausgabe 1986 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Pharmakokinetik Erfahrungen beim Menschen Tierexperimentelle Befunde Akute Toxizität Subakute Toxizität Chronische Toxizität Zur Frage eines MAK‐Wertes

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Butylated hydroxyanisole-stimulated NADPH oxidase activity in rat liver microsomal fractions.

Cited by 63 publications

References 11 publications

Radicals and melanomas

Radicals and melanomas

BHA and cancer risk : the role of prostaglandin H synthase in the carcinogenicity of butylated hydroxyanisole

Butylhydroxyanisol (BHA) [MAK Value Documentation in German language, 1986]

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