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.