Tobacco Documents Online

CFENLISTRY COWLTTEE • THE COUNCIL FOR TOBACCO RESEARCH - TT.S.A. SUCCESSOR TO THE TOBACCO INDUSTRY RESEARCH COMMITTEE Dr. Jacobson, Chm. Dr. Cattell Dr. Bing 1. Name of Investigator: John R. Rowlands . Date: May 27,. 1966 Senior Research Scientist . 3. Institution & Southwest Research Institut'e Address: 8500 Culebra Road San Antonio, Texas 78206 / C" 4. Project or Subject: A detailed investigation of the nature of the reaction between biological materials and atmospheric contaminants using Electron Paramagnetic Resonances and optical spectroscopic techniques is proposed. Such a program could lead to the development of experi- mental methods for assessing the relative importance of various atmospheric contaminants as biological hazards. In recent years a great amount of statistical information has leld to the belief that there exists a close relationship between cigarette smoking .and lung cancer. In addition, studies of this sort have also indicated a significantly higher incidence of lung cancer in areas of high atmospheric polution. - It has so far proven to be very difficult to establish in an objective way the nature of the effects of air polution~ and smoking because of the lack of a convenient experimental method. The advent of Electron Spin Resonance spectroscopy has provided ~ the most powerful experimental technique that is currently available for Q the detection:and identification of both free radicals and compounds con- Q taining pararnagnet'ic metals. The technique has been used with~ great CJ success in this last decade in such diverse areas as radiation biology, ~ chemical kinetics and providing important experimental parameters for ~ improving ligand field theory. Inst'ead of discussing in detail here the ~ experimental and theoretical aspects of electron paramagnetic resonance ~ we have included as appendices two reprints which indicate in some detail " the potential of the method. •.:..,_... ~:.,~:..... .. .. Detailed Plan of Procedure (Use additional pages if more space is required.) ' 633 T_IIIRD AVENIIE NE~y YOR.S. N. Y. 10017 Application For Research Grant I

In the course of studies sponsored' by.NCI involving the- chemical nature and properties of the constituents of tobacco smoke we have demonstrated that the reactive species found in the smoke interact quite dramatically with lung tissue to produce a complex elec-tron paramagnetic resonance signal. The cigarettes were smoked directly into freshly excised rabbit lung. Details of our experimental procedure and results will be published shortly. The most interesting feature of the results is that the resonance signal we observe is not just that of a free radical signal; but consists of both~ a free radical signal and a resonance which may be attributed to at least one type of' paramagnetic metal complex. No electron paramagnetic resonance signal was detected in control lungs under the same conditions used for the smoked lungs. The paramagnetic metal resonance signal does not exist in cigarette smoke itself and has obviously been produced~ by the reaction between cigarette smoke and lung tissue. We have not as yet identified the species giving rise to the signal but work is currently in progress in an attempt to make this identification. We have included as Figures 1, 2 and 3 the spin resonance signals of trapped cigarette smoke, a rabbit lung which has smoked six cigarettes and~ a rabbit lung which had smoked! no cigarettes. In a brief series of experiments we have also shown similar reactions of lung tissue with common atmospheric pollutant gases suggesting that a thorough investigation of the reaction between such contaminants and freshly excised lungs in addition to certain model biochemical systems such as metal-porphyrin complexes, has great promise in the study of the biological effect of atmospheric contaminants. It is suggested that the Council for Tobacco Research-U. S. A. will find in this experimental procedure a method which has the potential of allowing quantitative estimates of the biochemical (biological) effects of pollutants and further, of allowing a study of the combined biological effects off pollutants and tobacco smoke. •

See addenda for detailed breakdown for first year cost a. Salaries b. Expendable Suppljes c. Other Expenses d. Permanent Equipment e. Overhead (15% of a, b, c) 7. Anticipated Duration of Work: 3 years 8. Facilities and Staff Available: Total! In addition to the senior staff listed on the cost estimate and the few small items of equipment requested in the budget all the remaining facilities and personnel are available and~ will be assigned as requested. 9. Additional Requirements: 10. Additional Information (Including relation of work to other projects and other sources of support)! The proposed program is designed' to be complimentary to the existent NCI program entitled "Physical & Chemical Properties of Free Radicals and Alkylating Agents in Tobacco Smoke, " which deals explicitly with the effect of tobacco smoke alone. It is anticipated that in the latter phases of the proposed prograrn~ effortss will be devoted to the study of'the synergsstic effects of tobacco smoke coupled with atmospheric pollutants. Together these two programs should provide an excellent experimental approach to the vexing program to the connection between the breathing of contaminants of one form or another and the onset of lung cancers. In order to indicate the scope of our action in~ the approach of electron spin resonance to a variety of chemical and biochemical problems we have appended a partial listing of sponsored programs both completed and in progress. Signature / Directpr of Project Business Officer of the Institution W to

J. R Rowlands, Principle Investigator Research Scientist and Tech. Assistants Material and Supplies Animals and animal supplies Miscellaneous chemicals and glassware C. Other Expenses COST ESTIMATE First Year A. Direct Labor Cost r . Travel Expenses - Based on 2 Man Trips to New York Transportation 500 Subsistence - Based on 5 Man Days 100 Outside Consultant (Mr. Arthur Gross, 1250 Pico Laboratories) 10 days at $125/day Photography 250 Telephone Tolls and Telegraph 100 ` D. Surcharge ` Miscellaneous optical components for spectroscopic equipment Total Estimated Cost Signature Director of Project 2,200 20,878 2,000 $46, 058 1003546900 Business Officer of the Institution 110°fo Salaries Special Equipment

PREVIOUS AND PRESENT' PROGRAMS 4. Sponsor Rome Air Development Center 5: San Antonio R&D Pro- curement, Brooks AFB 6. 7. Corporation "Free Radicals in Paper by Electron Spin Resonance, '' 4-7-58 to 1-7-59. ` "Detection of Radiation Induced Free Radicals by Paramagnetic Resonance, Contract No. DA 19-129-QM-387, 5-18-55 to 10-18-57. "Detection of Radiation Induced Free Radicals by Paramagnetic Resonance, Contract No. 19-129-QM-10b0,. 11-14-57 to 7-13-59. "Investigation of Applications of Magnetic Resonance Absorption Spectroscopy to the Study of the Effects of Microwaves in Biologicali Materials, " Contract No. AF 30-(602)-1843, 5-1-58 to 5-1-59. "The Study of Radiation Induced Free Radicals in Chemical and Biological Systems, " Contract No. AF 41(657)-246, 8-1-58 to 10-29-63. Southwest Research "Basic Research-Free Radicals 'in, Institute Biological Materials," 8-28-57 to 1-31-58. - Thiokol Chemical "Devel~opment of Rapid! Methods and 8. Thiokol Chemical' Corporation Techniques for Analysis of Solid Propellants Based on Nuclear and Electron Paramagnetic Resonance, "' 10-31-57 to 12-8-58. "Electron Spin and Nuclear Spin Resonance Studies of PBAA Binder Systems„" 12-5-58 to 3-20-60. 9. Commercial Sponsor "Application of Magnetic Resonance Methods to the Study of Reaction Mechanisms Involving Free RadYcals, "' 9-1-59 to 12-31-61. 10. Quartermaster Corps "Study of Radiation Induced Reactions in Food Constituents by Resonance Methods," Contract No. DA 19-129-QM-1740, j 12-30-60 to 12-29-62. 1003546901

• San Antonio R&D Pro- curement Office, Brooks Air Force Base, Texas 12. Commercial Sponsor 13. Comrnerical Sponsor 14. Southwest Research Institute 15. Department of Health, Education & W elfare, Public Health Service 16. Brooks Air Force Base, Texas 17. Brooks Air Force Base, Texas 18. Food~ and Drug Administration 19. U. S. Army Dugway Proving Ground 20. Wright-Patterson AFB, Ohio Program "Thq Study of Radiation Induced Free Radicals in Chemical and Biological Systems," Contract No. AF 41(657)- 407, 8-f-51 to 11-30-63. "Application of Magnetic Resonance Methods to the Study of Energy Con- • version Processes of Photosynthesis," 9-1-59 to 12-31-62. "The Mechanisms and Inhibition of Enzyme Action by Electron Spin Resonance," 5-14-62 to 5-13-63. "An Electron Spin Resonance Study of Negative Ions of Porphyrins, 8-24-62 to 12-1-65. "Study of Radiation~ Damage Mechanisms to Biological Materialis,';' 10-1-65 to 9-30-68. "Determination of Free Radical Content in Chemical Systems, " Contract No. AF 41'(609)-2771, 2-15-65 to 3-11-66.. "The Effects of Ionizing Radiation on Oxidation States of Biological Systems," Contract No. AF 41(609)-2816,. 7-1-65 to 7-31-66. "'Investigation of Chemical-Eiectrical Sensing Methods for the Determination of Organ Phosphate Insecticides," Contract No. I?RO-C_. =63--105 (Neg. ) 6-3-63 to 6-2-64. "Design and Development of Electron Capture and Flame Ionization~ Techniques for Tracing Biological Aerosols in the Fie1d, " Contract No. DA 42-00'7-AMC-82(R), 1-29-64 to 7-1-65. "Analysis of Amino Acids by Gas Chroma- tography," Contract No. AF 33(6T5)-1823, 6-10-64 to 6-15-65. 1003546302

22. Southwest Research Institute 6-23-64 to 6-22-66. • 23. Ag riculture U. S. Department of "A Study of the Basic Methods of Action "The Correlation of Acetonitrile in Body Fluids to Tobacco Usage," 4-1-64 to 3-31-65. "Separation and Detection of Nitrogen Compounds of Biological Interest," - of' Several Fungicides Using Radio Frequency Absorption Methods, " Grant No. 12-14-100-802(34), 6-28-65 to 12-28-67. 24. Public Health~ Service "Radiation Damage Mechanisms in = Biological Materials, "' Grant No. RH GM 00384-01, 1-1-65 to 9-30-68. 25. National Institutes of "Physical & Chemical Properties of Health Free Radicals and Alkylating Agents in Tobacco Smoke," PH43-65-100, 6-23-65 to 6-22-66.

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