Document Type

Thesis - University Access Only

Award Date

2002

Degree Name

Master of Science (MS)

Department / School

Pharmaceutical Sciences

Abstract

Valluri, Hima Cancer is characterized by uncontrolled cell growth and invasion of adjoining cells. Among all types of cancers, skin cancer is the most common type of cancer. More than one million cases of basal-cell or squamous-cell cancers are diagnosed annually in the USA. Skin cancer attacks 1 out of 7 Americans every year. Studies have shown that there is an increased risk of other lethal cancer types of cancer in individuals with a history of skin cancer. Among all types of cancer, skin cancer is the most preventable cancer type. One approach to reduce the occurrence of skin cancer is through use of chemopreventive agents. A wide variety of chemopreventive agents have been investigated, which include both naturally occurring and synthetic compounds to prevent the occurrence of cancer. Among naturally occurring chemopreventive agents sandalwood (SW) oil was investigated in our laboratory. SW oil is extremely viscid, o( a light cream color and possesses a characteristically pleasant odor. SW oil has been used in India for the treatment of inflammatory and eruptive skin diseases for several centuries. a-Santalol obtained .from SW oil by distillation was investigated in our laboratory. Preliminary studies have shown the chemopreventive effects of a-santalol on 7,12-dimethylbenz(a)anthracene (DMBA) and 12-o-tetradecanoylphorbol-13-acetate (TPA) promoted skin cancer in CD-1 and SENCAR mice. The objective of the present investigation was to study the chemopreventive effects of a-santalol on DVB induced skin tumor development in female SKH-1 mice, and to determine the possible mechanism of action, by investigating the effect of asantalol pretreatment on TPA-induced and UVB induced ornithine decarboxylase (ODC) activity. A total of 180 female SKH-1 mice were used. According to skin tumor protocol, the mice were divided into 3 groups of sixty mice each. Each group is subdivided into two subgroups of thirty. The first subgroup served as control, and received acetone. The second subgroup served as experimental, and received a-santalol (5 % w/v in acetone). The first group mice were initiated with DVB-radiation and promoted with TP A. Prior to DVB-radiation mice received acetone or a-santalol. Second group mice were initiated with 7,12-dimethylbenz (a) anthracene (DMBA), and promoted with DVB radiation. Prior to UVB promotion mice received acetone or asantalol. Promotion phase continued for 25 weeks. The third group of mice were initiated and promoted with DVB radiation. Prior to DVB initiation and promotion mice were treated with acetone or a-santalol. ODC assay was performed to study the effect of a-santalol on TP A and UVB induced ODC activity in CD-1 mice (5-6 weeks old). Backs of the mice were shaved with electric clipper for topical application. The mice were divided into three groups containing three to five mice in each group. First and second group mice received TPA .Third group mice received acetone. After one hour of TPA / acetone treatment, mice in second and third groups received a-santalol and mice in first group received acetone. To know the effect of a-santalol on DVB-induced ODC activity mice were divided into three groups containing three to five mice in each group. Mice in first and second groups received DVB irradiation and mice in third group received acetone. After one hour of DVB / acetone treatment mice in second and third groups received a-santalol topical application and mice in first group received acetone. Distribution studies were performed in male Sprague-Dawley rat to explain whether chemopreventive effects of a-santalol are due to physical blockage or pharmacological interaction. The results suggest that topical administration of a-santalol significantly decreased DVB-induced skin papilloma incidence and multiplicity in SKH-1 mice .. Topical application of a-santalol one hour prior to TPA / DVB radiation reduced TP A/ DVB induced ODC activity in CD-I mice. Distribution studies indicate that chemopreventive effects of a-santalol absorption of are probably due to systematic absorption and pharmacological effect of a-santalol rather than blocking penetration of DVB radiation.

Library of Congress Subject Headings

Skin -- Cancer -- Chemoprevention Sandalwood oil Skin -- Cancer -- Animal models Mice -- Diseases

Format

application/pdf

Number of Pages

94

Publisher

South Dakota State University

Download

Share

COinS