Abstract B43: Dose-response on the chemopreventive effects of sarcophine-diol on UVB-induced skin tumor development in SKH-1 hairless mice.

Abstract

Abstract Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm2 UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm2. This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into 5 groups. The control group was topically treated with 200 μL of acetone (vehicle), and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone) 1 hour before UVB radiation (30 mJ/cm2). The last group of animals received 60 μg SD/200 μl acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were closely monitored as well. Histological characteristics and the proliferating cell nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose, reflected in reduced tumor multiplicities and tumor volumes. SD also reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD applications without UVB exposure had no effect on the structure of mice skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects. Citation Format: Ruth F. Guillermo, Xiaoying Zhang, Radhey S. Kaushik, David Zeman, Safwat A. Ahmed, Sherief Khalifa, Hesham Fahmy, Chandradhar Dwivedi. Dose-response on the chemo-preventive effects of sarcophine-diol on UVB-induced skin tumor development in SKH-1 hairless mice. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B43.