Photoprotective effects of some quinoxaline 1,4-dioxides in hairless mice

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 1998-12, Vol.15 (4), p.262-269
• Main Authors: GALI-MUHTASIB, H. U, HADDADIN, M. J, NAZER, M. Z, SODIR, N. M, MAALOUF, S. W
• Format: Article
• Language: English
• Subjects: Animals; Biochemical markers; Biological and medical sciences; Biomarkers, Tumor; Carcinogenesis, carcinogens and anticarcinogens; DNA - biosynthesis; DNA - drug effects; Enzyme Inhibitors - pharmacology; Enzymes; Female; Hairless; Immunotherapy; Male; Medical sciences; Metabolic activation; Mice; Mice, Inbred Strains; Mice, Nude; Molecular Structure; Neoplasms, Radiation-Induced - prevention & control; Oncology; Ornithine decarboxylase; Ornithine Decarboxylase - drug effects; Ornithine Decarboxylase - metabolism; Physical agents; quinoxaline; Quinoxalines - chemistry; Quinoxalines - pharmacology; Skin; Skin - drug effects; Skin - enzymology; Skin - radiation effects; Skin Neoplasms - prevention & control; Topical application; Tumors; U.V. radiation; Ultraviolet radiation; Ultraviolet Rays - adverse effects
• ISSN: 1357-0560; 1559-131X; 1432-0851
• DOI: 10.1007/BF02787210

2-benzoyl-3-phenylquinoxaline 1,4-dioxide (BPQ) and other substituted quinoxaline 1,4-dioxides (QdO) were tested for their ability to inhibit the stimulations of ornithine decarboxylase (ODC) enzyme activity and DNA synthesis, two biochemical markers linked to skin tumour promotion by ultraviolet B (UVB) radiation. Topical application of BPQ on the dorsal skin of hairless mice was found to inhibit in a dose-dependent manner UVB-induced ODC activity and DNA synthesis. When applied 20 min before UVB radiation, a dose of 17 mg BPQ applied in 0.4 ml of vehicle inhibited UVB-induced ODC activity and DNA synthesis by 95% and 85%, respectively. This inhibitory effect is dependent on the time of administration of BPQ relative to UVB radiation, with a generally greater inhibition observed when this compound is applied before rather than after UVB treatment. The inhibitory abilities of the other QdO on the ODC and DNA responses induced by UVB radiation greatly varied and appear to be dependent on the structure of the compounds and their metabolic activation in the skin following irradiation. The remarkable effectiveness of BPQ against the ODC and DNA markers of UVB promotion is also observed following multiple applications of this agent. These results suggest that QdO, in particular BPQ and certain derivatives of it, may be useful in protecting the skin against UVB-induced skin damage.