salicylates and Papilloma

The ability of a biomimetic superoxide dismutase agent, copper(II)(3,5-diisopropylsalicylate)2 (CuDIPS), to modulate benzoyl peroxide (BzPo)-induced tumor promotion and progression in mouse skin multistage carcinogenesis was evaluated. The results showed a significant inhibition of tumor incidence by CuDIPS pretreatment during promotion-progression. Different types of tumors were developed: papillomas, keratoacanthomas and squamous cell carcinomas. There was a significant increase in the keratoacanthoma-papilloma ratio when the period of treatment with BzPo was prolonged, which was inhibited by CuDIPS pretreatment. CuDIPS induced a significant inhibition of malignant conversion. Our results suggest that reactive oxygen species could be important in BzPo-induced promotion and progression.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Benzoyl Peroxide; Carcinoma, Squamous Cell; Cocarcinogenesis; Female; Incidence; Keratoacanthoma; Mice; Papilloma; Salicylates; Skin Neoplasms

A keratinocyte-mediated mutagenesis assay, and the murine skin multistage carcinogenesis tumor model were used to survey the chemopreventive properties of Cu(II)(3,5-diisopropylsalicylate)2 [CuDIPS] and its analogs. Supplementation of cocultures of newborn SENCAR keratinocytes and Chinese hamster lung fibroblasts (V79 cells) with CuDIPS, 3,5-diisopropylsalicylate (DIPS), and CuSO4 resulted in dose-dependent killings of V79 cells (LD50 of 34, 75, 960 microM, respectively), and inhibitions of benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) mutagenesis (ED50 of 13, 95, 80 microM, and 40, 125, 110 microM, respectively). Analyses of dose-response curves suggest (i) CuDIPS preferentially inhibits BP mutagenesis; (ii) the antimutagenic activity of CuDIPS towards DMBA and the cytotoxicity of the copper complex are derived from the DIPS component of the chelate; (iii) the antimutagenic activity of CuDIPS towards BP requires both copper and DIPS; and (iv) DIPS and CuDIPS induced cytotoxicity is required for inhibition of mutagenesis. Inhibition of mutagenesis by CuDIPS was not mediated by modulation of promutagen metabolism because antimutagenic concentrations of the chelate had no significant effects on DMBA- and BP-dependent cytotoxicities. Topical pretreatment of SENCAR mice with CuDIPS (100-4000 nmol) 15 min prior to initiation with DMBA or BP resulted in small (38% maximum) non-dose-responsive reductions of papillomas/mouse following 20 weeks of promotion.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Benzo(a)pyrene; Cell Line; Cell Survival; Cells, Cultured; Copper; Copper Sulfate; Epidermal Cells; Epidermis; Mice; Mice, Inbred Strains; Mutation; Papilloma; Salicylates; Skin Neoplasms

A low molecular weight, lipophilic, copper coordination complex with superoxide dismutase-mimetic activity inhibited biochemical and biological actions of a tumor promoter in mouse epidermis. Such inhibitory effects implicate reactive oxygen species in the tumor promotion process.

Topics: Animals; Antineoplastic Agents; Carcinogens; Female; Mice; Ornithine Decarboxylase; Papilloma; Salicylates; Skin Neoplasms; Superoxide Dismutase; Tetradecanoylphorbol Acetate

Topics: Age Factors; Antipyrine; Caffeine; Female; Humans; Kidney Failure, Chronic; Kidney Neoplasms; Kidney Pelvis; Male; Papilloma; Phenacetin; Salicylates; Sex Factors; Substance-Related Disorders; Sweden; Time Factors