Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-11-1
pubmed:abstractText
The modifying effects of topical application of the phenolic antioxidant protocatechuic acid (PA) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin tumor promotion were investigated. Dimethylbenz[a]anthracene-initiated female ICR mice were treated with TPA (1.6 nmol) twice weekly for 20 weeks to promote papilloma formation. Pre-treatment with 16nmol PA 30 min prior to each TPA treatment significantly inhibited the number of papillomas per mouse by 52% (P < 0.05). On the other hand, PA pre-treatment at a high dose (1600 nmol) significantly enhanced tumor numbers by 38% (P < 0.05). Interestingly, in the group treated with a quite high dose (20000 nmol) of PA 5 min prior to each TPA application, the average number of tumors per mouse was reduced by 38%, whereas the same PA dose 3 h before TPA treatment significantly enhanced tumor numbers by 84% (P < 0.01). These results suggested that topically applied PA was converted to compound(s) lacking antioxidative properties and/or rather possessing the potential to enhance tumor development. A similar tendency was also observed in the short-term experiment of TPA-induced inflammation and oxidative stress; i.e. two groups pre-treated with PA at 20000 nmol, 30min and 3h before TPA treatment, did not show suppression or even significantly enhanced TPA-induced leukocyte infiltration, H(2)O(2) generation, thiobarbituric acid-reacting substances level and proliferating cell nuclear antigen index, while PA treatment together with TPA significantly suppressed these parameters. Treatment with a high dose (20000 nmol) of PA alone for 3h enhanced oxidative stress by reducing glutathione levels in mouse skin, which was counteracted by the tyrosinase inhibitor arbutin. Oxidative stress responses such as leukocyte infiltration and H(2)O(2) generation were also counteracted by arbutin. These results suggested that tyrosinase-dependent oxidative metabolism of PA was at least partially involved in the enhanced effects of PA on TPA-induced inflammatory responses and thus tumor promotion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/9,10-Dimethyl-1,2-benzanthracene, http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxybenzoic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Monophenol Monooxygenase, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/protocatechuic acid
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1899-907
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11023549-9,10-Dimethyl-1,2-benzanthracene, pubmed-meshheading:11023549-Animals, pubmed-meshheading:11023549-Antioxidants, pubmed-meshheading:11023549-Biotransformation, pubmed-meshheading:11023549-Carcinogens, pubmed-meshheading:11023549-Dermatitis, Contact, pubmed-meshheading:11023549-Dose-Response Relationship, Drug, pubmed-meshheading:11023549-Drug Administration Schedule, pubmed-meshheading:11023549-Drug Synergism, pubmed-meshheading:11023549-Female, pubmed-meshheading:11023549-Glutathione, pubmed-meshheading:11023549-Glutathione Peroxidase, pubmed-meshheading:11023549-Glutathione Transferase, pubmed-meshheading:11023549-Hydrogen Peroxide, pubmed-meshheading:11023549-Hydroxybenzoic Acids, pubmed-meshheading:11023549-Mice, pubmed-meshheading:11023549-Mice, Inbred ICR, pubmed-meshheading:11023549-Monophenol Monooxygenase, pubmed-meshheading:11023549-Oxidative Stress, pubmed-meshheading:11023549-Papilloma, pubmed-meshheading:11023549-Skin, pubmed-meshheading:11023549-Skin Neoplasms, pubmed-meshheading:11023549-Tetradecanoylphorbol Acetate
pubmed:year
2000
pubmed:articleTitle
A simple phenolic antioxidant protocatechuic acid enhances tumor promotion and oxidative stress in female ICR mouse skin: dose-and timing-dependent enhancement and involvement of bioactivation by tyrosinase.
pubmed:affiliation
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't