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HT®0121111 7. Other a. Review Article Title: BIOLOGICAL ACTIVITY OF CIGARETTE SMOKE CONDENSATE (CSC) AND CSC FRACTIONS (CSCF) A uthors: C.J. Henry, M.D. Avery, T.J. Henry, and R.E. Kouri Proposed outline of chapter. I. Introduction A. Definition B. Preparation of whole CSC C. Review of chemical composition of CSC D. Fractionation of CSC E. Identification of classes of constituents or individual consituents of CSC II. Short Term Assays with CSC and CSCF A. Introduction B. Mutagenesis C. Transformation D. Direct effe^ts on DNA E. Organ culture F. Sebaceous gland G. In Vivo activation III. Conclusions A. Advantages/disaCvantages of short term assays to evaluate CSC B. Interpretation of results relating to biological ef fects of CSC S tatus: Draft scheduled 12/81. ;I 3

HT®0121112 b. Human AHH (1) Title: POSITIVE CORRELATION BETWEEN HIGH ARYL HYDROCARBON HYDROXYLASE ACTI- VITY AND PRESENCE OF LUNG CANCER - ANALYSIS IN CRYOPRESERVED LYMPHO- CYTES Authors: R.E. Kouri, C.E. McKinney, D.J. Slomiany, D. Snodgrass, N.P. Wray, and T.L. McLemore SUMMARY Aryl hydrocarbon hydroxylase (AHH) activity, NADH-depen- dent cytochrome c reductase (Cyt c) activity, and rate of 3H-thymidine incorporation were determined in cryopreserved lym- phocytes taken from individuals hospitalized for symptoms of re- spiratory distress. A total of 67 samples were collected -- 13 were contaminated, and one did not mitogen activate. Of the total of 52 individuals who were analyzed, a total of 21 lung cancers were diagnosed with the remaining individuals expressing a variety of diseases including COPD, pneumonia, and tuberculo- sis. AHH/Cytc activities in these individuals were related to the presence of lung cancer. Of the fourteen highest AHH/Cytc activities observed, all were found in patients with lung cancer. Mean AHH activities for all lung cancer patients were 0.89 units AHH/Cytc while that of non-lung cancer patients were 0.47 units AHH/Cytc (p 4.001). There was no relationship between AHH activities and histologic type of cancer, age of the patient, cigarette smoking history, family history of cancer, or levels of 3H-thymidine incorporation. Results are discussed with the view that the presence of the lung cancer may influence the expression of AHH activity associated with the peripheral blood lymphocytes. Status: Submitted to Cancer Research 7/81. i s- 3V

H1®0121113 (2) Title: A METHOD FOR DETECTING ARYL HYDRO- CARBON HYDROXYLASE ACTIVITIES IN CRYOPRESERVED HUMAN LYMPHOCYTES Authors: R.E. Kouri, J. Oberdorf, D.J. Slomiany, and C.E. McKinney SUMMARY Aryl hydrocarbon hydroxylase (AHH) activity, NADH-depen- dent cytochrome c reductase (cyt c activity, and 3H-Thym- idine (3h-TdR) incorporation were-monitored in human lymphocytes cryopreserved for periods up to one yee.r. A standard procedure for freezing, thawing, and culturing of these lymphocytes was developed. Kinetics for expression of benz(a)anthracene-induced AHH activity, cyt c activity, and 3H-TdR incorporation were similar in both freshly cultured and cryopreserved cells. Lyr~- phocyte samples from ten indivudlas were collected once per month over a three month period and cells were either cultured at tne time of donation or cryopreserved for later assay. Results indi- cated that the cryopreserved lymphocytes efficiently responded to mitogen activation, the intra-individual variation in AHH activi- tes was reduced in the cryopresered lymphocytes compared to the freshly cultured cells, and the relative ranking of these indivi- duals in terms of their AHH activities remained constant for both fresh and cyropreserved samples. Cryopreservation seems to offer significant advantages over the freshly cultured lymphocytes because it allows for lymphocyte samples to be collected in di- verse geographical locations and over extended periods, of time and yet permits for the culture and assay of all the cell samples at exactly the same time. Status: Accepted Cancer Letters, 8f81. Z~ 1

HT®0121114 c. XTV Studies Title: XENOTROPIC VIRJS EXPRESSION AND SUSCEP- TIBILITY TO 3-METHYLCHOLAhTHRENE-INDUCED CANCER Authors: K.T. Nayar, J.A. Levy, B. O'Neill, and R.E. Kouri SUMMARY I This paper reports the lack of genetic linkage between spontaneous production of substantial amounts of infectious xeno- tropic (X-tropic) virus and the susceptibility to chemically induced cancers ir. two inbred strains of mice, NZB/BLNJ and 129/3, and their genetic crosses. The parental strains and Fl, backcross, and F2 progeny between these two strains were partial- ly splenectomized to ascertain X-tropic viral status and were subsequently treated s.c. with 500 ug of 3-methycholanthrene in trioctanoin. Progeny from second backcrosses [(F1 x 129) x 129] were also tested for their X-tropic viral status and susceptibi- lity to 3-methylcholanthrene carcinogenesis. Mice were observed for evidence of fibrosarcumas at the site of inoculation over a 10-month period. In this genetic system, spontaneous production of high titers of X-tropic virus segregated as a single autosomal dominant gene. Susceptibility to 3-methylcholanthrene induced fibrosarcomas did not segregate in these crosses, and suscepti- bility did not correlate with the degree of X-tropic virus expression. Status: Published, Cancer Res. 40: 4364-4367, 19806 26

HT®U121115 d. SUMMARY Effects of Sendai Virus Title: EFFECTS OF SENDAI VIRUS AND VACCINE ON SHORT-TERM TOXICOLOGICAL AND IMMUNOLOGI- CAL MARKERS IN STRAIN A/J MICE Authors: C.J. Henry, M.J. Collins, W.C. Hall, D. Putman, R.A. Lubet, D.R. Dansie, M.D. Avery, C. McKinney, and R.E. Kouri Over the last several years, we have noticed that inad- vertent infection with Sendai virus can alter interpretaion of the results of chemical carcinogen bioassays in three major ways: 1) reduced survival during chemical treatment, 2) alteration in the latency and incidence of chemically induced pulmona ry car- cinomas, and 3) appearance of alveol.ar epithelial hypertrophy and hyperlasia. During prelimnary cigarette smoke inhalation stud- ies, we observed that Sendai virus infection completed the mor- phologic appearence and interpretation of pulmonary lesions. Following vaccination against Sendai virus, we noticed that sur- vival increased, that dose-response became prodictable, and that proliferative alveolar epithelial lesions were reduced. What has been lacking in this area is a controlled study investigating the effects of Sendai virus and the recently developed vaccine on defined short-term and long-term end-points in a model system for chemical carcinogensis. The following study has been implemented to address the effects of Sendai virus and vaccine on a battery of short-term markers in Strain A/J mice. Upon receipt of the animals. the mice were tested and found to be negative for serum anitbody titers to Sendai virus. The mice were divided into four groups: untreated, Sendai virus infected, Sendai vaccinated, and Sendai vaccinated and infected. The vaccinated mice were immunized with Sendai virus 3 weeks prior to initiation of experimentation. Mice were lightly anesthetized and given one LD of Sendai virus (Strain P3193) intranasally. Animals were killio on days 2, 5, 9, 14, and 21. The following assays were determined in each group: a) mitogen activation of spleen cells using concanavalin A, phytohemagglutinin, and E. coli lipopolysac- cha r i de; ~ b) Jerne plaque cell forming (PFC) assay to sheep red blood cells (SRBC) at 3. 5, and 7 days post SRBC immunizatiions; 4

NT®0121116 c) pulmonary and hepatic aryl hydrocarbon hydroxylase levels; d) pulmonary and hepatic ornithine decarboxylase levels; e) serum antibody titers against Sendai virus; f) lung virus levels; and g) histopathology of the respiratory tract. Results will be presented. 0 Status: Proc. Amer. College Vet. Path. (in press), 1981; first draft of manu- script scheduled for 12/81. 12/81.