Tobacco Documents Online

HTE0120044 t ( Fig. 1(b) Weltoa ezposute chamber. One ride plate has been temoved to ahos' the inafds 'a[ e:posute chamber (CH) with the cou:ca4ehoped esposure holes (H) visible. Duuing an espoaute the ciprette dome (D'. movee forward and automatically fgnitee the cigarette (C). and 35 ml of puff air is [oreed through the cigetatte into tbo chembar. A continuously rotating [en (F) ie tequirtd to ®tume rapid and uniform mixing of the smoke. At the end of an e:poaur® Intervall. emok+l Is aenred through ohe exlmuat port (E). -9-

H T®0120045 Figure 2. The SEM II with front and side panels open to show electronic components. See text for full operational details. Cigarettes (C) are loaded from a hopper (HO) into a rotating drum holder (DH). The lighter (L) automatically ignites the cigarette and puff air is forced through each cigarette in turn. Flow is caused by a constantly held differential pressure provided by the positive pressure in the dome (D0) between the ignited end and the butt end of the cigarettes. Dilution air (DA) is introduced at the butt end of the ~,iga- rette. Side stream smoke is removed through the vent (V). Cigarettes are removed by the automatic ejector (E) and discarded in the butt shutte (S) -10-

Figure 2 HtC0120U4b -11-

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HT§0120048 ( Figure 4. SEM II animal containment system. One side of the unit isshown,with the capacity for exposing 240 mice per side (480 mice total). Rubber stoppers are used in the exposure holes when less than the full capacity of mice are to be exposed. -13-

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H1Mp120050 X. BIBLIOGRAPHY The appendix attached to this document contains selected references that highlight some of the scientific contributions of Microbiological Associates in the areas of toxicology and carcinogenesis research. Reprints of papers most salient to application of the lung cancer model system and nose-only Inhalation ara also included. -15-

Y H T O01 20051 ( APPENDIX I k

HTE0120052 l l PUBLICATIONS Kouri, R.E., Salerno, R.A., and Whitmire, C.E. - Relationships between Aryl Hydrocarbon Hydroxylase Inducibility and Sensitivity to Chemically-Induced Subcutaneous Sarcomas in Various Strains of Mic.e. J. Natl. Cancer Inst., 50: 363-368, 1973. Kouri, R.E., Ratrie, H., and Whitmire, C.E. - Evidence for Genetic Relationship Between Susceptibility to 3-Methylcholanthrene Induced Subcutaneous Tumors and Inducibility of Aryl Hyd:ocarbon Hydroxylase. J. Natl. Cancer Inst., 51: 197-200, 1973. Lubet, R.A., Brown, o.Q., and Kouri, R.E. - The Role of 3-OH-Benzo(a)pyrene in Mediating Benzo(a)pyrene Induced Cytotoxicity and Transformation in Cell Culture. Res. Comm. in Chem. Path. and Pharm., 6: 929-942, 1973. Oemoise, C.F., Kouri, R.E., and Whitmire, C.E. - Cell-Mediated Immunity After Intratracheal Exposure to 3-Methyicholanthrene and its Relationship to Tumor Transplant Growth in C3H/f Mai Mice. In: E. Karbe and J.F. Park (Eds.) Experimental Lung Cancer. Springer- Verlag, New York, p. 72, 1974. Kouri, R.E., Ratrie, H., and Whitmire, C.E. - Genetic Control of Susceptibility to 3-Methytcholanthrene-Induced Subcutaneous Sarcomas. Int. J. Cancer, 13: 714-720, 1974. Nebert, D.W., Benedict, W.F., and Kouri, R.E. - Aromatic Hydrocarbon Produced Tumorigenesis and the Genetic Differences in Aryl Hydrocarbon Hydroxylase Induction. In: P. Ts'o and J. DiPuolo (Eds.) Chemical Car0nogenesis, Part A., Marcel Dekker, New York, pp. 271-288, 1974. Benedict, W.F., Rucker, N., Mark, C., and Kouri, R.E. - Correlation Between the Balance of Specific Chromosomes and the Expression of Malignancy in Hamster Cells. J. Nat1. Cancer Inst., 54: 157-162, 1975. Benedict, W.F., Rucker, N., Faust, J., and Kouri, R.E. - Malignant Trans- formation of Mouse Cells by Cigarette by Cigarette Smoke Condpnsate. Cancer Res., 35: 857-860, 1975. Kouri, R.E., Whitmire, C.E., and Benedict, W.F. - In Yivo and In Vitro Effects of Cigarette Smoke Condensate Fractions. Proc. M-Assoc. Cancer Res., 16: 173, 1975. Kouri, R.E., Rude, T., Thomas, P.E., and Nhitmire, C.E. - Studies on Pulmonary Aryl Hydrocarbon Hydroxylase Activity in Inbred Strains of Mice. Chem. 8io1. Interactions, 13: 317-331, 1976. Kouri, R.E. - Relationship Between Levels of Aryl H,vdrocarbon Hydroxylase Activity and Susceptibility to 3-Methylcholanthrene and Benzo(a)pyrene Induced Cancers in Inbred Strains of Mice. In; Polynuclear Aromatic Hydrocarbcns: Chemistry, Metabolism and Carcinogenesis. Freudenthal & Jones, (Eds.) Raven P-ess, New York, p. 139-151, 1976. i

HTE0120053 ( Kouri, R.E., Imblum, R.L., and Prough, R.A. - Measurement of Aryl Hydro- Carbon Hydroxylase and NADH-Dependent Cytochrome c Reductase Activities in Mitogen-Activated Human Lymphocytes. Proc. 3rd Intl. Symp. on Detection and Prevention of Cancer, H.E. Nieburgs (Ed.) Marcel Dekker, Nerr York p. 510, 1977. Kouri, R.E., and Nebert, D.W. - Genetic Regulation of Susceptibility to Polycyclic Hydrocarbon-Induced Tumors in the Mouse. In: Origins of Human Cancer, H.H. Hiatt, J.D., Watson, and J.A. Winsten, (Eds.) Cold Spring Harbor Press, p. 811-835, 1977. Nebert, O.W., Boobis, A.R., Yagi, H., Jerina, D.M., and Kouri, R.E. - Genetic Differences in Benzo(a)pyrene Carcinogenic Index In Vivo and in Mouse Cytochrome P 450-Mediated Benzo(a)pyrene Metahol~te Binding to DNA In Vitro. In: Biological Reactive Intermediates, D.J. Jallow, J. J. Kocsis, R. Snyder, and H. Vainio, (Eds.) Plenum Press, New York, 1977. Schechtnian, L.M., and Kouri, R.E. - Control of Benzo(a)pyrene-Induced Mammalian Cell Cytotoxicity, Mutagenesis, and Transformation by Exogenous Enzyme Fractions. In: Progress in Genetic Toxicology D. Schoot, B.A. Bridges, F.H., Sobels, (Eds.) Elsevier/North Holland Press, New York, Vol. 2, p. 307, 1977. Billups. L.M., Henry, C.J., Whitmire, C.E., and Kouri, R.E. - Pathogenesis of Chemically Induced Lung Lesions in Mice. Proc.Am. Assoc. Cancer Res., 19: 142, 1978. Nebert, D.W., Atlas, S., Guenther, T., Kouri, R.E. - The Ah Locus: Genetic Regulation of the Enzymes wnich Metabolize Polycyc)ic Hydrocarbons and the Risk of Cancer. Polycyclic Hydrocarbons and Cancer: Chemistry Molecular Biology and Eniironment, P.O.P. Ts'o and H.V. Gelboin, (Eds.) Academic Press, New York, p. 345-390, 1978. Radtke, H.E., Rude, T., and Kouri, R.E. - Evidence of Heterogeneity of Hepatic and Pulmonary Epoxide Hydratase (EH) Activity in Inbred Strains of Mice. Proc. Am. Assoc. Cancer Res.,19: 142, 1978. Henry, C.J., Billups, L.H., Avery, M.D., Dansie, D.R. Lopez, A., Breth, L.A., Rude, T.R., Kouri, R.E. - Lung Cancer Model Systems in Inbred Strains of Mice. Proc. Am Assoc. Cancer Res., 20: 242, 1979. Henry, C.J., Lopez, A., Whitmire, C.E., Caton, J., Henderson, C.M., Kouri, R.E. Deposition and Distribution of Total Particulate Matter (TPM) in BC3F1 Mice After Exposure to Cigarette Smoke. Toxicology & Applied Pharmacology,48: A5, 1979. Kouri, R.E., Kurtz, S., Vernon, M.L., Schechtman, L.M., Nicholson, M., Klement, V., and Benedict, W.F. - C-Type RNA Virus from Hamster Cells Transformed In Vitro by 1-B-D-Arabinofuranosylcytosine. Arch. of Vi.ology,62: NT--252, 19'9. ii