Detail of "2216-94-6"

Reference

Effects of combined treatments with selenium, glutathione, and vitamin E on glutathione peroxidase activity, ornithine decarboxylase induction, and complete and multistage carcinogenesis in mouse skin

Effects of combined treatments with selenium, glutathione, and vitamin E on glutathione peroxidase activity, ornithine decarboxylase induction, and complete and multistage carcinogenesis in mouse skin. Perchellet, Jean Pierre; Abney, Nancy L.; Thomas, Ryan M.; Guislain, Yvette L.; Perchellet, Elisabeth M. (Anti-Cancer Drug Lab., Kansas State Univ., Manhattan, KS 66506, USA). Cancer Res., 47(2), 477-85 (English) 1987. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Section cross-reference(s): 1, 18 Several structurally different tumor promoters altered to various degrees both glutathione peroxidase (EC 1.11.1.9) [GSH peroxidase] [9013-66-5] and L-ornithine decarboxylase (EC 4.1.1.17) [ODC] [9024-60-6] activities in mouse epidermis in vivo. At 5 h after their application to the skin, the complete tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) [16561-29-8] and the stage 2 promoter mezerein [34807-41-5] were the most potent in inhibiting GSH peroxidase activity and inducing ODC activity. In comparison, the effects of anthralin [1143-38-0], phorbol 12,13-didecanoate [24928-17-4], benzoyl peroxidase [94-36-0], H2O2, and phorbol 12,13-dibenzoate [25405-85-0] were much smaller, whereas the nontumor promoter phorbol [17673-25-5], the hyperplastic agent ethyl phenylpropiolate [2216-94-6], and the stage 1 promoter 4-O-Me TPA [57716-89-9] did not alter GSH peroxidase and ODC activities. Various treatments including i.p. injections of 40 mg of Na2SeO3 and 100 mmol of reduced glutathione (GSH) [70-18-8] and/or topical applications of 40 mmol of D-a-tocopherol (vitamin E) [59-02-9] 20 or 15 min, resp., before tumor promoter treatment inhibited in an additive manner the effects of either TPA or mezerein on both GSH peroxidase activity and ODC induction. Moreover, these Na2SeO3, GSH, and/or vitamin E treatments inhibited in the same additive manner the tumor-promoting activity of TPA in the initiation-promotion protocol. However, when tested in the 2-stage promotion protocol with 4 doses of TPA followed by twice weekly applications of mezerein, Na2SeO3 plus vitamin E and GSH plus vitamin E treatments inhibited remarkably the tumor-promoting activity of mezerein but were ineffective in the first stage of promotion. The sequence and magnitude for the effects of 7,12-dimethylbenz[a]anthracene (DMBA) [57-97-6] on GSH peroxidase and ODC activities were very different from those of the tumor promoters. In contrast with their antitumor-promoting activity, the treatments with Na2SeO3 plus vitamin E and GSH plus vitamin E failed to inhibit the carcinogenicity of a single large dose of DMBA and even enhanced the induction of skin tumors by repeated applications of subcarcinogenic doses of DMBA. Apparently, the promoting component of DMBA carcinogenesis may be different from that of TPA. Moreover, the anticarcinogenicity of Na2SeO3, GSH, and vitamin E may be linked to their ability to facilitate or enhance the activity of the natural GSH-dependent antioxidant protective system of the epidermal cells during the later stages of skin tumor promotion.

Non-promoting hyperplasiogenic agents do not mimic the effects of phorbol 12-myristate 13-acetate on terminal differentiation of normal and transformed human keratinocytes

Non-promoting hyperplasiogenic agents do not mimic the effects of phorbol 12-myristate 13-acetate on terminal differentiation of normal and transformed human keratinocytes. Parkinson, E. Kenneth; Emmerson, Ann (Med. Sch., Univ. Birmingham, Birmingham B15 2TJ, UK). Carcinogenesis (London), 5(5), 687-90 (English) 1984. CODEN: CRNGDP. ISSN: 0143-3334. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The effects of the potent tumor promoter PMA (I) [16561-29-8] and 2 nonpromoting hyperplasiogenic compds. Et phenylpropriolate (EPP) [2216-94-6] and the divalent cation ionophore A 23187 [52665-69-7] on the terminal differentiation of normal and transformed human keratinocytes were studied by using the loss of cloning efficiency and the formation of cornified envelopes as markers of the differentiated state. PMA induced terminal differentiation in a far greater proportion of normal keratinocytes than it did in the squamous cell carcinoma line SCC-27 but EPP and the Ca ionophores A 23187 and Br X537A [38784-08-6] had no such differential effect, possibly explaining the poor promoting ability of the last 3 compds.