Effect of Sidestream and Mainstream Smoke Exposure on in Vitro Interferon-A/Fl Production by L-929 Cells'

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ICANCERRESEARCH46, 2779â€”2783,June1986J Effect of Sidestream and Mainstream Smoke Exposure on in Vitro Interferon-a/fl Production by L-929 Cells'

Gerald Sonnenfeld2 and Russell W. Hudgens Departments ofMicrobiology and immunology and Oral Biology, Schools ofMedicine and Dentistry. University ofLouisvile. Louisville, Kentucky 40292

ABSTRACF tion by L-929 cells. The highest doses of smoke that induced minimal mortality of the cells were used (12). In addition, A peristaltic pump smoking machine that allows simultaneous gener smoke was manipulated by delaying the time of exposure of ation of mainstream (active) and sidestream (passive) smoke from a cells after smoke generation (aging) and by passage of smoke cigarette was used to expose cultures of murine L-929 cells, a potent producer of interferon, to smoke. The cigarette used was the University through activated charcoal. The results of the present study of Kentucky 2R1 reference cigarette. The dosages of smoke used for indicate that smoke exposure can inhibit IFN induction in L exposure were the highest doses possible that generated a minimum toxic 929 cells. The degree of inhibition of IFN induction was much effect, and they were serially diluted to lower doses. Dosages were greater than inhibition that could be accounted for by loss of determined by the number of smoke puffs generated, the volume of smoke viable cells in the smoke-exposed cultures. In addition, manip puffs generated, and the total particulate matter deposited on Cambridge ulations of smoke that decreasedtoxicity to L-929 cells (I 2) filters in the smoke machine. Viability of exposed cells was equivalent to and to yeast (13, 14) also decreased the inhibition of IFN control cell cultures. Interferon-a/fl was induced by addition of polyri induction after smoke exposure. boinosinic-polyribocytidylic acid to the cells. Interferon production was substantially reduced in viable cells exposed to mainstream or sidestream smoke. Aging of smoke by delaying time of exposure of the cells to the MATERIALS AND METHODS smoke, or filtration of smoke through activated charcoal substantially decreased the alteration of interferon production by smoke exposure. CellCultures. L-929 cells were originally obtained from the American These results suggest that actual exposure of cells to mainstream or Type Culture Collection (Rockville, MD) and were maintained in MEM sidestream smoke can inhibit in vitro interferon-a/ft induction, but the (GIBCOLaboratories,GrandIsland,NY) supplementedwith10%fetal cells can be protected from these effects by smoke manipulation. bovineserum.All cultureswereplatedin 25-cm2plastictissueculture flasks (Falcon Plastics, Oxnard, CA). Cultures were utilized for expo INTRODUCTION sure experiments upon reaching confluency (I). Interferon Induction. Mouse IFN-a//3 was induced in cultures of L Several studies have indicated that IFN-a/f33 production was 929 cells as previously described (11). Briefly, 50 @zgofpoly-rI.rC (P inhibited by pretreatment of cell cultures or animals with car L Biochemicals, Milwaukee, WI) were used. One hundred @igofDEAE cinogens (1â€”5).Treatment of cell cultures or animals with dextran (Pharmacia Fine Chemicals, Piscataway, NJ) were added to each culture to ensure maximum IFN induction (6). After the initial 1- poorly or noncarcinogenic analogues had no effect on IFN h period of incubation, sufficient MEM was added to the cultures to induction (1â€”5).These studies have been recently extended to bring them to a final volume of 2 ml. The cultures were next incubated include inhibition of murine in vitro and in vivo IFN induction for 23 h at 37T in 5% CO2. Culture supernatant fluids were then by carcinogenic chemical components of cigarette smoke (6, 7); harvestedandassayedforantivirusactivity. however, cigarette smoke is composed of a complex mixture of Interferon Assay. The antivirus activity of putative IFN samples was chemicals in solid and vapor phases, and the effects of individual determined by means of a plaque reduction assay utilizing the Indiana components may not mirror the effect of actual smoke on IFN strain of vesicular stomatitis virus as the test virus (15). L-929 cell production (8, 9). cultures were the target cells for the IFN assay. The IFN titer corre Recently, a new exposure machine utilizing a peristaltic pump spondedto the reciprocalof the greatestdilutionof test samplethat mechanism has been developed (10). This machine allows the reduced virus plaquing by 50%. In this assay system, one antivirus unit simultaneous exposure of animals or tissue cultures to both of IFN was equivalent to 0.88 NIH G-002-904-5l 1 reference standard units. mainstream (active) and sidestream (passive) smoke (10). Uti Smoke Exposures. The peristaltic pump smoking machine, provided lizing this exposure system, we have recently studied the effects by the Kentucky Tobacco and Health Research Institute, was utilized of cigarette smoke on viability of L-929 cells in culture (1 1). for all exposurestudies(10). A completedescriptionof the system, We have shown that either mainstream or sidestream smoke including diagrams and photographs, has been previously published in exposure resulted in dose-dependent mortality to the cells. Ref. 10. This machine generates smoke through a puffing mechanism, Dilution, aging, and filtration of the smoke through activated and mainstream smoke is pumped directly to an exposure system able charcoal each decreasedthe toxic effects of the mainstream or to expose four tissue culture flasks at the same time. Sidestream smoke sidestream smoke exposure on L-929 cells (12). was trapped off the end of a burning cigarette in a plastic chamber and The current study was designed to determine the effects of pumped to an additional exposure system capable of exposing four mainstream or sidestream smoke exposure on IFN-a/fl produc tissue culture flasks at the same time. In this fashion, tissue cultures were exposed to mainstream and sidestream smoke generated from the Received 11/20/85; revised 2/27/86; accepted 3/5/86. same cigarette. The cigarette used was the University of Kentucky 2Rl The costs of publication of this article were defrayed in part by the payment reference cigarette (16). The cigarettes were not selected for weight or of page charges. This article must therefore be hereby marked advertisement in pressure drop. TPM for each cigarette exposure was determined by accordance with 18 U.S.C. Section 1734 solely to indicate this fact. @ Supported by a grant from the Kentucky Tobacco and Health Research extracting Cambridge filters placed in the path of smoke with acetone Institute. measuring the absorbance of an extract at 390 nm, and multiplying the 2To whom requests for reprints should be addressed, at Department of results by the dilution factor (10). Mainstream smoke was generated at Microbiology and Immunology, School of Medicine, University of Louisville, a rate of one puff per mm with a puff duration of 2.4 s. Puff volume Louisville, KY 40292. 3 The abbreviations used are: IFN, interferon; MEM, minimal essential me averaged17ml and wasobtainedby useof a calibrateddilution tip dium; poly-rIrC, polyriboinosinic-polyribocytidylic acid; TPM, total particulate placed at the top of the puff chamber (10). The smoke exposure matter. apparatus was washed with 70% ethanol to decrease the possibility of 2779 Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1986 American Association for Cancer Research. TOBACCO SMOKE AND IFN

contamination. All medium was removed from the tissue culture flasks ulations were carried out using four puffs of sidestream smoke. andreplacedwith 4 ml of MEM. The tissuecultureflaskswerefitted Passageof smoke through charcoal filters or aging of smoke onto the apparatus, and a tight seal was obtained (10). The cultures prior to exposure ofcells to sidestream smoke yielded low levels were next exposed to smoke as will be described for each individual of toxicity to the cells (Table 1). experiment. â€œShamâ€•exposure was obtained in some instances by pass Cultures ofconfluent L-929 cells were exposed to mainstream ing air through the system to the tissue cultures. After exposure, the cells were returned to a 37'C incubator with 5% CO2for 1 h. Then, the smoke. Exposure of cells to greater than eight puffs of smoke medium was removed from each flask and was replaced with 2 ml of resulted in appreciable mortality to the cells (Table 2). Exposure MEM with 2% fetal bovine serum. Twenty-four h later, IFN was of cells to up to six puffs of mainstream smoke resulted in a induced, and the cells were allowed to incubate for another 24 h. Then, lesser degree of mortality to the cells, so all additional main culture supernatant fluids were harvested and assayed for IFN antivirus stream smoke manipulations were carried out using an exposure activity, and viability was determined by means of a trypan blue dye of six puffs. Manipulation of smoke through charcoal filters or exclusion assay. In this study, the percentage of mortality is defmed as aging of mainstream smoke resulted in decreased mortality of L-929 cells as measured by trypan blue viability staining. â€” . (control viability sample viability) % ofmortality = ... x 100 In addition, cells that were exposed to dosages of smoke that (control viability) produced minimal mortality were harvested from the cell cul ture plates. These cells were then diluted, replated, and repli (10). Smoke Manipulation. Aging ofsmoke was obtained by placing plastic cated at the same rate as control unexposed cells (data not chambers of different size between the smoke source and the tissue shown). cultureflask.This servedto delaythe timeof exposureof the cellsto Effect of Sidestream Smoke Exposure on IFN Induction. Cell the smoke after the generation of smoke. Filter studies were carried cultures were exposed to four puffs of sidestream smoke, and out by placing filters between the puffchamber and the peristaltic pump then IFN-a//3 was induced with poly-rI .rC. The number of for mainstream smoke exposure, and between a dilution chamber and exposures for each type of treatment is indicated in Table 1. the peristaltic pump for sidestream smoke exposure. The acetate filters Smoke-exposed cell cultures produced 60% less IFN than did were similar in design to those used in actual cigarettes, and they were nonexposed control cultures, while mortality of the exposed contained in a plastic holder designed to permit the introduction of cells was only 9% (Fig. 1). Cells exposed to seven puffs of activated charcoal (10). sidestream smoke produced no detectable IFN, but since via Statistical Analysis. Data were analyzed by means of Student's t test with a set a priori at P < 0.05. bility was decreased by 99%, this was probably due to cell death (Fig. 1).

RESULTS TableL-929cells 2 Tolalparticulate matter depositedandpercentage ofmortality of exposed to 50% ofmainstream smoke generatedfromcigaretteTPM a 2R1 Parameters of Smoke Exposure. Cultures of confluent L-929 (mg) Mean% cells were exposed to smoke generated from a 2R1 reference ofTreatment mortalityNone n CF@la CF-4 cigarette burned in the peristaltic pump smoking machine. Cells 0â€œShamâ€• 16 0 0 were exposed to either 40% of the sidestream smoke generated 02Puffs smokeexposure 4 0 0 or 50% ofthe mainstream smoke generated.Cells were exposed 84 20 1.9 3.3 to increasing numbers of puffs of cigarette smoke. Exposure 226PuffsPuffs 12 4.2 8.3 248 16 7.5 12.9 data from cells exposed to sidestream smoke with TPM mdi 476Puffs 7 9.2 17.2 cated are shown in Table 1. Each experiment represents the 86Puffs,followedby 2-s delay 4 7.9 12.4 96Puffs,followedby 4-s delay 4 7.7 12.9 exposure offour replicate cultures to smoke. Exposure of smoke 96Puffs,followedby 8-s delay 4 7.7 12.5 up to four puffs of sidestream smoke resulted in minimal 26filter6Puffs, followed by acetate 4 5.7 9.9 mortality of the cells (Table 1). All mortality studies were 9charcoal6Puffs, followed by 25 mg 4 4.2 7.1 performed using a trypan blue dye exclusion assay. Exposure of cells to sevenpuffs or more of sidestream smoke resulted in 6charcoal6Puffs, followed by 50 mg 4 3.0 6.9 high mortality to the cells (99%); therefore, all smoke manip 8charcoalPuffs, followedby 100 mg 4 4.0 8.0 TableL-929cells I Totalparticidate matter depositedandpercentageofmortality of exposed to 40% ofsidestream smoke generatedfromcigaretteTPM a 2R1 a CF-I, Cambridge filter collecting mainstream smoke in the postexposure position; CF-4, Cambridgefilter collectingmainstream smoke not reaching the (mg) Mean% exposurechamber.For detailsofexposure system,see Ref. 10. ofTreatment mortalityNone n CF-V CF-3 @lOOF 04Puffs 4 0 0 Id 97Puffs 4 1.0 2.5 F- 99lOPuffs 4 1.8 4.3 I- 9913 4 3.6 6.4 z 994Puffs 4 4.4 7.7 LA. 144Puffs, followedby 2-s delay 8 1.1 2.7 -J 94Puffs,foHowedby8-sdthyPuffs, followedby 4-s delay 8 1.4 2.6 0 164 8 1.3 2.5 F- 28filter4Puffs, followed by acetate 4 0.6 4.2 z 0 C) 18charcoal4Puffs, followed by 25 mg 4 0.6 3.9

+ 9charcoal4Puffs, followed by 50 mg 4 0.7 3.5 @1@..@ 0 4 7 3charcoalPuffs, followedby 100 mg 4 0.7 4.0 PUFFS OF SMOKE Fig. 1. Effect ofexposure of L-929 cells to different numbers of puffs of 40% a CF-2, Cambridge filter collecting sidestream smoke in the postexposure ofgenerated sidestream smoke on IFN induction by poly-rI .rC. 0, cells exposed position; CF-3, Cambridgefilter collecting sidestream smoke not reaching the to sidestreamsmoke; @,statisticallysignificantdecreasein titer from unexposed exposure chamber. For details ofexposure system, see Ref. 10. control cells t, data not interpretable because of high mortality of cells. 2780

An exposure of four puffs of sidestream smoke, followed by aging of smoke by delaying the time of delivery ofsmoke to the Iii cells, altered the effects of sidestream smoke on IFN produc Iâ€” tion. Delaying of smoke exposure for 2 or 4 s still resulted in I, inhibited IFN-a//3 production (Fig. 2). An 8-s delay in smoke z @7I exposure resulted in the smoke losing its capacity to signifi cantly inhibit IFN production (Fig. 2). @.1 0 50 Filtration of smoke through activated charcoal also resulted I-. z in alterations of the effects of sidestream smoke on IFN induc 0 tion. Passage of the sidestream smoke through acetate filters U prior to exposure of cells still resulted in an inhibition of IFN 25 induction in the exposed cells (Fig. 3). Passage of smoke through 25 or 50 mg of activated charcoal also still resulted in inhibition of IFN induction in sidestream smoke-exposedcells; 0 however, passage of sidestream smoke through 100 mg of PUFFS OF SMOKE activated charcoal resulted in an abrogation of significant in Fig. 4. Effect ofexposure of L-929 cells to different numbers of puffs of 50% hibition of IFN induction by sidestream smoke (Fig. 3). ofmainstream smokegeneratedon IFN inductionbypoly-rI.rC. 0, cellsexposed to mainstreamsmoke;*,statisticallysignificantdifferenceintiter fromunexposed Effect of Mainstream Smoke Exposure on IFN Induction. control cells. Cells were exposed to six puffs of mainstream smoke, and then IFN was induced by addition of poly-rI . rC. The number of exposures for each type of treatment is indicated in Table 2. J00 This treatment resulted in inhibition of IFN induction (Fig. 4). Ui Greater puff numbers also resulted in inhibition of IFN induc Iâ€” F- tion, but with unacceptable levels of mortality (Fig. 4); there z 75 fore, dosagesof six puffs of mainstream smoke were used in LA.

smoke manipulation experiments. Sham exposure ofcells, plac 50 I- z 0 C) 25 I00

75 0 2 4 8 AGEOFMAINSTREAMSMOKE(SEc@ z U- Fig. 5. Effectof agingon mainstream smoke on IFN induction.Six puffsof 50% of mainstream smoke generated were used in all experiments. 0, direct SO exposure of cells to mainstream smoke; 0, aging of smoke by delaying the time of exposure of cells to mainstream smoke; @,statistically significant decrease in titer compared to unexposedcontrol cells. I- z 0 25 0 ing the cell cultures in the exposure system and passingair over them, had no effect on IFN induction (Fig. 4). When mainstream smoke was aged by delaying the time of 0 2 4 8 exposure of cells to the smoke, a 2-s delay of exposure yielded AGE OF SIDESTREAM SMOKE (SEC) some loss of capacity of the smoke to inhibit IFN induction Fig. 2. Effect of aging of sidestream smoke on IFN induction. Four puffs of (Fig. 5). Aging of smoke for 4 or 8 s resulted in a loss of 40% of sidestream smoke generated were used in all experiments. 0, direct exposure of cells to sidestream smoke; 0, aging of smoke by delaying time of capacity of mainstream smoke to inhibit IFN induction in the exposureof cellsto sidestreamsmoke; , statisticallysignificantdecreasein titer exposed L-929 cells (Fig. 5). compared to unexposed control cells. When mainstream smoke was passagedthrough acetate fil ters, a surprising result was observed. IFN production was l00 actually enhanced when L-929 cells were exposed to main stream smoke filtered through acetate (Fig. 6). Passage of mainstream smoke through 25 mg ofactivated charcoal did not affect the capacity of the smoke to inhibit IFN induction (Fig. 5). Filtration of mainstream smoke through 50 or 100 mg of @: / activated charcoal did remove the capacity of the smoke to significantly alter IFN production in exposedcells (Fig. 6).

DISCUSSION

@ @N0@25@0 I@0 FILTER Carcinogenic components of both mainstream and side mc CHARCOAL IN FILTERS stream cigarette smoke havebeenshown to inhibit both in vitro Fig. 3. Effectof filtration of sidestreamsmoke on IFN induction. Four puffs and in vivo murine IFN-a/fl production (6, 7). This is in of 40% of sidestream smoke generated were used in all experiments.0, direct accordance with the general observation of inhibition of IFN exposure of cells to sidestreamsmoke; V, passageof smoke through a cellulose filter, L,@,passageof smoke through activated charcoal; @,statistically significant induction by carcinogens and the lack of effect of poorly or decrease in titer compared to unexposed control cells. noncarcinogenic analogues (1â€”5).Since tobacco smoke is made 2781

role for toxic effects other than those detectable by trypan blue staining cannot be ruled out; however, since cells exposed to smoke and shown to be viable by trypan blue dye exclusion did not grow at a rate different from unexposed cells, it seems likely

Id that effects of smoke other than direct toxicity to the cells play F- a major role in the inhibition of IFN induction. F- z To further study this problem, various types ofsmoke manip LI. ulation were carried out. Passageof sidestream smoke through activated charcoal resulted in the smoke losing the ability to

F- inhibit IFN induction. In addition, aging of sidestream smoke z 50 0 resulted in the smoke losing the ability to inhibit IFN induction. C) These results, similar to those observed in yeast studies and in 11 L-929 cell toxicity studies (12â€”14),suggestthat the vapor phase of the sidestream smoke may play some role in the observed effects. The results of these experiments also suggest that Â°NO 0 25 50 similar manipulations of smoke can reduce genetic alterations FILTER mg CHARCOAL IN FILTERS of yeast, toxicity to mammalian cells, and inhibition of IFN induction. Fig. 6. Effect of filtration of mainstream smoke on IFN induction. Six puffs of 50% of mainstream smoke generated were used in all experiments. 0, direct The situation with mainstream smoke is less clear. Main exposureof cells to mainstream smoke;V, passageof smoke through an acetate stream smoke exposure decreasedIFN induction in L-929 cells filter, t@,passage of smoke through activated charcoal; , statistically significant in a dose-dependentfashion; however, the effects were far less difference in titer from unexposed control cells. striking than those observedwith sidestream smoke. Aging of smoke did result in the mainstream smoke losing capacity to up of a complex mixture of components in addition of carcin inhibit IFN induction. Filtration of the mainstream smoke ogens(8), the questionstill could be askedif actualcigarette through acetate filters surprisingly yielded an enhancement of smoke exposure could affect IFN induction? IFN production in exposed cells. In previous toxicity studies, Earlier studies have shown that exposure of yeast (Saccha filtration of mainstream smoke through acetate filters did not romyces cerevisiae) to mainstream smoke resulted in genetic affect the mortality generated in the cells after mainstream effects occurring in the yeast (13, 14). These effects included a smoke exposure (12). The increase in IFN production in cells 5-fold increase in mitotic gene conversion and increases in exposedto smoke passedthrough acetatefilters may havebeen reverse mutation frequency and mitotic crossing over (13, 14). in part due to the presenceof tumor promoters in mainstream The generation of these effects of mainstream smoke was smoke (9). Tumor promoters havebeen shown to enhanceIFN dependent on the dosageof smoke used. In addition, filtration induction (18). Enhanced IFN production could be considered of the smoke through activated charcoal decreased the activity pathological, as evidenced by spontaneous IFN production in of the smoke in this system in proportion to the amount of individuals with acquired immunodeficiency syndrome (19). charcoal used (13, 14). Preliminary data from our laboratory also suggest that mice The recent development of the dual-exposure (mainstream exposed to mainstream smoke may in some instances exhibit and sidestream smoke) peristaltic pump smoking machine has enhanced IFN production. allowed the extension of these smoke exposure studies to mam Passage of mainstream smoke through activated charcoal malian systems (10, 12).Recently, we have shown that exposure resulted in the smoke losing the ability to inhibit IFN induction of L-929 cells to mainstream or sidestream smoke resulted in in a fashion dependent on the amount of charcoal used. This the generation of mortality in the cells (12). The degree of again suggeststhat manipulation ofsmoke by charcoal filtration mortality generated was dependent on the dosage of smoke can result in the restoration ofnormal IFN responsesin exposed used (12). In addition, filtration of smoke through activated cells. charcoal or aging of smoke by delaying the time of exposure of The nature of the interactions between tobacco smoke and the cells to the smoke decreasedthe mortality observed (12); the IFN system appears to be complex. Many parallels appear therefore, the results obtained observing toxicity of smoke to to exist between the results observed with effects of smoke on L-929 cells were ofa similar pattern to those obtained observing mortality of cells and effects of smoke on IFN induction. genetic alterations of yeast after smoke exposure (I 2â€”14). Further experimentation is under way to delineate the param In the present study, L-929 cells were exposed to sidestream eters and significance of these interactions, and to definitively or mainstream smoke to determine the effects of exposure on identify the components of smoke responsible for the observed IFN-a/$ production. Exposure of cells to sidestream smoke effects. resulted in a decreasein IFN production. A dosage of smoke that induced minimal toxicity, four puffs of 40% sidestream ACKNOWLEDGMENTS smoke generated, was chosen for the majority of studies. Treat ment of cells with that dose of sidestream smoke resulted in The authors thank Dr. Robert B. Griffith of the University of mortality ofonly 9%, but a decreasein IFN production of 60%. Kentucky College of Pharmacy for his extremely helpful suggestions, We havepreviously shown that a reduction in viable cell number comments, and criticisms that were applied to the execution of these experiments and the writing of this paper. of 50% is required for a 50% decrease in IFN production (17); therefore, it is unlikely that a 9% decreasein the number of viable cells could account for a 60% decreasein IFN production. REFERENCES Small changes in viability observed after exposure of cells to 1. Barnes,M. C., Streips, U. N.. and Sonnenfeld.G. Effectofcarcinogens and smoke that has undergone aging or filtration are unlikely to analogs on interferon induction. Oncology (Basel), 38: 98â€”101,1981. account for the observedalteration of interferon production. A 2. DeMaeyer, E., and DeMaeyer-Guignard, J. Inhibition by 3-methylcholan 2782

threne of interferon formation in rat embryo cells infected with Sindbis virus. exposure systems. 1. Equipment and procedures. Toxicology, 34: 123â€”138, J. Natl. Cancer Inst., 32: 1317â€”1321,1964. 1985. 3. DeMaeyer-Guignard, J., and DeMaeyer, E. Effect of carcinogenic and non 11. Dianzani, F., Cantagalli, P., Gagnoni, D., and Rita, C. Effect of DEAE carcinogenic hydrocarbons on interferon synthesis and virus plaque devel dextran on production of interferon by double-stranded RNA in L-cells. opment. J. Nail. Cancer Inst., 34: 265â€”276,1965. Proc. Soc. Exp. Biol. Med., 128:708â€”711,1968. 4. Hahon, N., Booth, J. A., and Stewart, J. D. Aflatoxin inhibition of viral 12. Sonnenfeld, G., Griffith, R. B., and Hudgens, R. W. The effect of smoke interferon induction. Antimicrob. Agents Chemother., 16: 277â€”282,1979. generation and manipulation variables on the cytotoxicity of mainstream and 5. Sonnenfeld,G., Hudgens,R. W., and Streips, U. N. Effectof environmental sidestream cigarette smoke to monolayer cultures of L-929 cells. Arch. carcinogens and other chemicals on murine alpha/beta interferon production. Toxicol., 58: 120â€”122,1985. Environ. Res., 31: 355â€”361,1983. 13. Gairola, C. Genetic effects of fresh cigarette smoke in Saccliaromyces cere 6. Sonnenfeld,G. Effect of sidestream tobacco smoke components on alpha! visiae. Mutat. Res., 102: 123â€”136,1982. beta interferon production. Oncology (Basel), 40: 52â€”56,1983. 14. Gairola, C., and Griffith, R. B. Recombinogenic activity of fresh cigarette 7. Sonnenfeld, G., and Hudgens, R. W. Effect of carcinogenic components of smoke in Saccharomyces cerevisiae. Cancer Detect. Prevent., 4: 53â€”57,1981. tobacco smoke on in vivo production of murine interferon. Cancer Res., 43: 15. Hanna, C., Merigan, T. C., and Jawetz, E. Inhibition of TRIC agents by virus-induced interferon. Proc. Soc. Exp. Biol. Med., 122: 417â€”422,1966. 4720-4722, 1983. 16. Huber, G. L., and Vaught, A. The Reference Cigarette. Lexington, KY: 8. Brunnemann, K. D., Adams, J. D., Ho, D. P. 5., and Hoffman, D. The Kentucky Tobacco and Health Research Institute, 1979. influence of tobacco smoke on indoor atmospheres. II. Volatile and tobacco 17. Golemboski, K. A., and Sonnenfeld, G. Reversibility of inhibition of inter specific nitrosamines in main- and sidestream and their contribution to feron-alpha/beta induction by benzo(a)pyrene. J. Nail. Cancerlnst., 73: 763â€” indoor pollution. In: Proceedings of the Fourth Joint Conference on Sensing 766, 1984. of Environmental Pollutants, pp. 876â€”880.New Orleans, LA: American 18. Vilcek, J., Yip, Y. K., Stone-Wolff, D. S., and Pang, R. H. L. Stimulation of Chemical Society, 1978. gamma interferon production by TPA and related diterpene esters. Texas 9. Hoffman, D., Hecht, S. S., and Wynder, E. L. Tumor promoters and Rep. Biol.Med., 41: 108â€”115,1982. cocarcinogens in tobacco carcinogenesis. Environ. Health Perspect., 50: 245- 19. Eyster, M. E., Goederty,J. J., Poon, M.-C., and Preble, 0. 1. Acid-labile 257, 1983. alpha interferon. A possible preclinical marker for the acquired immune 10. Griffith, R. B., and Hancock, R. Simultaneous mainstream-sidestream smoke deficiency syndrome in hemophelia. N. EngI. J. Med., 309: 583â€”586,1983.

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Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1986 American Association for Cancer Research. Effect of Sidestream and Mainstream Smoke Exposure on in Vitro Interferon-α/β Production by L-929 Cells

Gerald Sonnenfeld and Russell W. Hudgens

Cancer Res 1986;46:2779-2783.

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