The broad goal of this research is to gain a better understanding of the molecular basis for the dermatological phototoxicity of the tetracycline family of drugs. These drugs, among the most widely prescribed family of antibiotics, represent a virtually classic example of such phototoxicity. The objectives of the program include the complete delineation of (a) tetracycline's unimolecular photochemistry and (b) the covalent binding of tetracycline photoproducts to nucleic acids. Specifically, the program will (1) complete the identification of """"""""lumitetracycline"""""""", a new photoproduct isolated in these laboratories which gives evidence for possible greater phototoxicity than tetracycline itself, (2) determine the mechanistic details of tetracycline's photochemistry, (3) identify the photoproducts formed from tetracycline which covalently bind to DNA in the dark, (4) determine the bases which are the targets for such binding and the chemical reactions involved and (5) extend our studies to the photochemistry and photobiology of lumitetracycline in order to establish the origin of this molecule's recently determined mitochondrial phototoxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR039286-04
Application #
3159292
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1988-05-01
Project End
1993-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Shea, C R; Olack, G A; Morrison, H et al. (1993) Phototoxicity of lumidoxycycline. J Invest Dermatol 101:329-33