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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1983-7-8
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pubmed:abstractText |
The relationship between reactive oxygen and/or free radical species and tumor promotion was evaluated by investigating the inhibitory effects of 2(3)-tert-butyl-4-hydroxyanisole (BHA) and other antioxidants on the induction of ornithine decarboxylase (ODC) activity in mouse epidermis by a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice maintained on a diet containing 0.75% BHA for 8 days showed a 50% reduction in maximal ODC induction following treatment with TPA when compared to mice fed a control diet. Topical application of BHA (55 mumol) 30 min prior to TPA treatment (17 nmol) elicited an 80% inhibition of promoter-induced ODC activity. BHA was ineffective as an inhibitor when administered either 16 hr before or 2 hr after the promoter. The inhibition by BHA was dose dependent with a dose producing a 50% inhibition of ODC induction of 6 mumol. A structure-activity study with BHA analogues (2-tert-butyl-4-hydroxyanisole, 3-tert-butyl-4-hydroxyanisole, 2-tert-butyl-1,4-dimethoxybenzene,tert-butylhydroquinone, 4-hydroxyanisole, p-hydroquinone, phenol, and 2-tert-butyl-phenol) showed that hydroxyl and tert-butyl substituents were important determinants of inhibitory activity. A spectrum of other antioxidants were also tested. Butylated hydroxytoluene was nearly equipotent to BHA; alpha-tocopherol, propyl gallate, and disulfiram were all less potent, and L-ascorbate was inactive. None of the antioxidants affected basal ODC activity in non-TPA-treated mice. Collectively, these results demonstrate an early and direct inhibition of TPA-induced ODC activity by lipophilic phenolic antioxidants and suggest a role for reactive oxygen and/or free radical species in tumor promotion.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anisoles,
http://linkedlifedata.com/resource/pubmed/chemical/Butylated Hydroxyanisole,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxy-Lyases,
http://linkedlifedata.com/resource/pubmed/chemical/Ornithine Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbols,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2555-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:6850576-Administration, Topical,
pubmed-meshheading:6850576-Animals,
pubmed-meshheading:6850576-Anisoles,
pubmed-meshheading:6850576-Butylated Hydroxyanisole,
pubmed-meshheading:6850576-Carboxy-Lyases,
pubmed-meshheading:6850576-Dose-Response Relationship, Drug,
pubmed-meshheading:6850576-Enzyme Induction,
pubmed-meshheading:6850576-Epidermis,
pubmed-meshheading:6850576-Female,
pubmed-meshheading:6850576-Mice,
pubmed-meshheading:6850576-Ornithine Decarboxylase,
pubmed-meshheading:6850576-Phorbols,
pubmed-meshheading:6850576-Tetradecanoylphorbol Acetate,
pubmed-meshheading:6850576-Time Factors
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pubmed:year |
1983
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pubmed:articleTitle |
Inhibition by 2(3)-tert-butyl-4-hydroxyanisole and other antioxidants of epidermal ornithine decarboxylase activity induced by 12-O-tetradecanoylphorbol-13-acetate.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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