Induction of epidermal proliferation and expressions of PKC and NF-kappaB by betel quid extracts in mouse: the role of lime-piper additives in betel quid.
Components of betel quid (BQ) have been investigated for genotoxicity, mutagenicity, and animal toxicity. However, little information exists regarding their carcinogenic characteristics. Considerable attention has already been focused on tumor promoters that occur environmentally for human uptake. In this study, the promoting effects of BQ and lime-piper additives (LPA) in BQ on epidermal hyperplasia in CD-1 mouse skin are investigated. In the present study, we found that BQ and LPA at concentrations of 25,50,75 mg/ml caused significant induction of hyperplasia, but only LPA caused an increase of epidermal ornithine decarboxylase (ODC). Treatment of mouse skin with LPA caused remarkable increases in the production of H(2)O(2) by 2.41-, 3.90-, and 3.76-fold (for the above-indicated concentrations respectively); as well as marked increases of myeloperoxidase (MPO) by 1.43-, 2.70-, and 2.29-fold. Application of LPA or BQ (50,100,150 mg/ml) also caused induction of protein kinase C-alpha (PKC-alpha) and NF-kappaB. LPA exhibited more significant effect than BQ. Thus, LPA might make a major contribution to the BQ-induced expression of PKC and NF-kappaB. These results indicated that BQ has the potential of being promoting agents, and that LPA should play a major role in increasing the effects of BQ-caused skin hyperplasia and inflammation. The promoting effects of BQ and LPA on mouse skin were associated with the induction of the expressions of PKC and NF-kappaB.
Lee
Miao-Jane
MJ
Institute of Biochemistry, Chung Shan Medical University, No. 110, Section 1, Chien-Kuao N. Road, Taichung 402, Taiwan.
Hsu
Jeng-Dong
JD
Lin
Chiann-Ling
CL
Lin
Ming-Hsun
MH
Yuan
Shu-Chuan
SC
Wang
Chau-Jong
CJ
D000818:Animals; D001114:Areca / Q000009:adverse effects* / Q000737:chemistry; D015153:Blotting, Western; D017610:Calcium Compounds / Q000009:adverse effects* / Q000737:chemistry; D002273:Carcinogens / Q000009:adverse effects* / Q000737:chemistry; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis*; D010087:Oxides / Q000009:adverse effects* / Q000737:chemistry; D009195:Peroxidase / Q000096:biosynthesis; D031701:Piper; D010936:Plant Extracts / Q000009:adverse effects* / Q000737:chemistry; D011493:Protein Kinase C / Q000096:biosynthesis*
D017610:Calcium Compounds; D002273:Carcinogens; D016328:NF-kappa B; D010087:Oxides; D010936:Plant Extracts; C495400:lime-piper betel quid; D006861:Hydrogen Peroxide; C016538:lime; D009195:Peroxidase; D011493:Protein Kinase C