Characterization of the tumor-promoting activity of m-chloroperoxybenzoic acid in SENCAR mouse skin and its inhibition by gallotannin, oligomeric proanthocyanidin, and their monomeric units

Abstract

m-Chloroperoxybenzoic acid (CPBA),which induces ornithine decarboxylase activity as much as 12-O-tetradecanoylphorbol-13-acetate (TPA), was tested for its ability to induce DNA synthesis, hydroperoxide (HPx) production, and tumor promotion in mouse epidermis in vivo. After an early inhibition, CPBA stimulates DNA synthesis, a response which is maintained between 16 and 72 h and maximal after two treatments. CPBA at 0.6-5 mg stimulates DNA synthesis more than other organic peroxides, and nearly as much as TPA. The HPx-producing activity of the epidermis is maximally stimulated 48 h after two CPBA treatments at a 24-h interval. However, the HPx response to CPBA is much smaller than that to TPA. Aleppo gall tannic acid (AGTA) and loblolly pine bark condensed tannin (LPCT) inhibit both the DNA and HPx responses to CPBA. In contrast, their respective monomeric units, gallic acid (GA) and catechin (Cat) inhibit the DNA response to CPBA but fail to alter CPBA-stimulated HPx production. Although it is more potent than benzoyl peroxide, CPBA is a complete tumor promoter much weaker than TPA and even less effective than mezerein (MEZ). CPBA in stage 1 cannot enhance like TPA the tumor-promoting activity of MEZ in stage 2. And in contrast to that of MEZ, the very weak tumor-promoting activity of CPBA is not enhanced after stage 1 treatment with TPA. At equal mg doses, AGTA, GA, LPCT, and Cat pretreatments all remarkably inhibit complete skin tumor promotion by CPBA. In spite of their antioxidant activities, AGTA post-treatments have no or very little inhibitory effects on the development of skin tumors by CPBA during 2-stage or complete tumor promotion.