Document reY3eqrapn7k4KanXnrbLQ56G

I'oloiiium-210! A Volatile amount of undigested material remains. In these artificial smoking experi Kiulioeleraent in Cigarettes Nevertheless, we have recovered near ments, the following portions of the ly 100 percent of polonium added to cigarette and smoke were analyzed for Abstract. Polonium-2 JO, which emits cigarettes during digestion, the same re polonium: the. ash and butt of the ciga elpha particles, is a natural contaminant covery as that for teeth and bones (J). rette; smoke condensate on the fiber tobacco. For an individual smoking Polonium samples were counted in gas- glass and HA filters; condensate that two packages of cigarettes a day, the flow proportional counters with back formed on the tubing and metal parts radiation dose to bronchial epithelium ground counts of alpha particles in the of the filter holder and on the walls of from Po" inhaled in cigarette smoke range of 0.5 to 1.5 count/hr. We have the .liter bottle, all of which were care probably is at least seven times that confirmed that the radioactivity plated fully wiped after the cigarette was front background sources, and in local on silver with the initial separation is smoked; and the HCI trap through ized areas may be up to 1000 rem or Po212 by observing its decay, which has which the filtered air had been drawn. more in 25 years. Radiation from this closely conformed to the Po210 half-life Blank analyses on filters, trap solution, source may, therefore, be significant in of 138 days. and wipings of the tubing, filter holder, the genesis of bronchial cancer in This report deals only with the and bottle showed no polonium activ smokers. polonium content of cigarettes and ity with the exception of the fiberglass cigarette smoke. The cigarettes we used filters, which had approximately 0.015 Although it is well known that ioniz were four of the regular-sized Ameri pc of Po2"1. The HA filter and HCI trap ing radiation is carcinogenic in man can brands purchased in local stores. showed little or no polonium after (/), there has been no evidence that The smoke from cigarettes puffed smoking, and in the results the content radioisotopes in cigarettes are impli artificially was obtained by drawing air observed on the fiberglass (usually cated in the production of lung cancer. through cigarettes connected to a filter about 90 percent of the total) was com Measurements of potassium-40 and holder. This holder contained a fiber bined with that from the condensate radium isotopes have been made in glass prefilter (6) backed by a Milli- and HA filter. tobacco (2, 3) but these elements are pore HA filter that retains 100 percent Table 1 shows the polonium content not volatile at the temperature of a of the particles in the size range of of whole cigarettes of four brands.- burning cigarette--600C to 800C tobacco-smoke particles (7). The fiber Also given are the contents of the ash, (4)--and therefore cannot deliver any glass prefilter actually collected nearly butt, and total smoke when all of the significant radiation dose. Turner and all of the smoke and was used to pre smoke, including the side stream, was Radley (3) measured total alpha-par vent rapid clogging of the HA filter. trapped. Included in Table I are the ticle activity in raw tobacco and ciga From the filter holder, gas from the results for mainstream smoke alone col rette ashes, and concluded that the dose smoking cigarette was led through a lected in different experiments. Table derived from radon and its daughter trap containing 50 ml of 0.5 normal 1 indicates that only about half the products would be less than 1 percent HCI, then to a rotameter connected to polonium in the total smoke was in the of that of the normal background to a vacuum line. When the cigarette was mainstream when cigarettes were puffed tbc bronchial epithelium. Our studies smoked artificially it was in a nearly by our technique. When all the smoke were undertaken to reevaluate the con vertical position. The vacuum line was was captured, about 80 percent of the centration of alpha-emitting radioele- clamped off between puffs, and during polonium disappearing in the smoking ments in cigarettes. In our experiments each puff the flow rate was maintained process could be accounted for. These "'e have found in tobacco significant at 15 ml/sec for 2 to 3 seconds. The results suggest that most of the volatile amounts of Po2I", which we believe to puffs were carried out every 50 sec- polonium is rapidly adsorbed on the be in equilibrium with its parent Pb210. ,, onds for 6 minutes (or eight puffs); smoke particles, although a small part A substantial part of this polonium Ap this puffing pattern was the average of could be gaseous and escape our trap pears in cigarette smoke, and on the that, observed without their knowledge, ping procedure, including the HCI trap. basis of certain assumptions we calcu for a number of smokers in our lab Because of the nature of the smoking late that polonium may constitute a oratory, and is similar to that reported pattern that was used, we believe that 'ignificant initiator of neoplasia in the by Hiding (8). It resulted in consump the mainstream smoke is probably low bronchial epithelium of a cigarette tion of about 60 to 70 percent of the in these experiments, compared to ac smoker. cigarette, or somewhat less than that tual smoking conditions. For example, The methods we have used for sepa observed in cigarettes smoked by the higher concentrations in the butt of rating radium isotopes and Po2I have human subjects. Side stream smoke brand D, Table 1, indicate that these been described previously (5). Briefly, (smoke not drawn through the cig cigarettes were not as completely 'be sample is treated with hot concen arette) was captured by placing a liter smoked as the others. For this reason trated HC1 (wet-ashing), the polonium bottle over the burning cigarette. Air no significance can be attached to dif 'S plated on silver, and the radium iso- and smoke in the bottle were continu ferences in mainstream content between !"pes are then coprecipitated with lead ously drawn through the same filter filter and nonfilter brands. When ciga 'ulfatc and barium sulfate. We have system as the mainstream smoke, but rettes were smoked by human subjects :,ot found it necessary to modify our the tube from the bottle was clamped the polonium content of the butt and r"utine procedure in separating polo- only during puffing, when the tube ash was lower than that of the arti mum or radium from cigarettes, al- from the cigarette was open. In this ficially smoked cigarettes, and the pro 1 bough with digestion by hot concen way both side stream and mainstream portion of polonium lost from the ciga trated HCI, solution of cigarettes or smoke were trapped together on the rette was higher for filter cigarettes. ' 'b is incomplete and a considerable filters. We suspect that the amount of polon- >7 JANUARY 1964 247 Table 1. Polonium content of American cigarettes and smoke from cigarettes artificially puffed. Figures in parentheses are number of analyses. cumulated in these regions, and on. the mean residence time occurring in such Whole cigarette l>o=10 content (pc) Ash Butt Total smoke Total in ash, butt, and smoke Recovery* m Po*0 in main stream smoke (pc) Ratio of main stream to total smoke <%> cases. There is no quantitative basis on which to estimate these two factors in human lungs, but it is likely from our preliminary measurements of po lonium in the bronchial epithelium of lungs of smokers, that these local doses may range from several hun 0.43(4) 0.031(2) 0.13(2) Brand A, nonfiUer 0*19(2) 0.35 81 0.10(3) dred rem to more than 1000 rem, in 52 the case of an individual smoking two 0.48(5) 0.053(2) 0.12(2) Brand B, nonfiller 0.26(2) 0.43 90 0.12(2) packs a day over a 25-year period. For 46 example, in a 73-year old male who 0.39(4) 0.035(2) 0.094(2) Brand C, filter 0.19(2) 0.32 died of cardiac failure, who had 82 0.088(2) 47 smoked "one or more" packs of cig 0.40(4) 0.033(2) 0.15(2) Brand Z>, filter 0.17(2) 0.35 88. 0.070(3) arettes per day for many years, the 41 polonium content in the epithelium of Ratio of total in ash, butt, and smoke to total in whole cigarette. a secondary bifurcation of the right lower lobe was 0.033 pc/cnr, com pared with 0.003 pc/cnr in the rigid ium absorbed by an individual may be alpha particles, in accord with recom main stem bronchus. This man had dependent on the mode of puffing as mendations of the International Com not smoked after hospital admission well as on. the fraction of total smoke mission for Radiation Protection (14). -for smoke inhalation 10 days prior to inhaled. The radiation dose delivered by death, and he had evidence of bron The alpha-emitting isotopes we have polonium inhaled from cigarettes can chial pneumonia at autopsy, so it is investigated all occur naturally, and be analyzed for two conditions. The probable that equilibrium concentra presumably have always been present first condition defines approximately tion of polonium in the epithelium at in tobacco. Absorption of Pb"", the the minimum radiation dose to be ex the time he was smoking was substan parent of Po", by the plant roots may pected; in this ease the dose arises tially higher. Even so, a level of 0.033 be supplemented by foliar absorption from particles carried across the pc/cm2 would give a dose of 165 rem from "natural fallout" from decay of bronchial epithelium in the process of in 25 years. This figure is a minimum Rnm in the atmosphere (9). From excretion by mucus flow up the vatue even for this region of epithe analysis of 5-year-old cigarettes, we bronchial tree. The smoke particles lium, and higher values could also be conclude that the amount of polonium are assumed to be deposited by diffu present in heavier smokers. Further in fresh whole cigarettes (Table 1) is sion, largely on the alveolar epithelium, work will be required to determine in equilibrium with the Pb" parent. from where they are phagocytosed and these local doses, particularly through With respect to radium and polonium carried up the bronchial epithelium use of quantitative radiographs. content, tobacco appears to be typical of (75). In this case we estimate that the With regard to the amount of po plants generally, as judged by the total minimum dose delivered by these parti lonium absorbed into the circulation alpha-particle activity found in plants cles for an individual smoking two from tobacco smoke, compared to po by Mayneord et al. (10). The radia packages of cigarettes a day for 25 lonium absorbed from other sources, tion hazard from Po*" arises primarily years would be about 36 rem (16) or it is of interest that the urine of non- because polonium is known to be com seven times the background exposure. smokers contains very little polonium pletely volatile above 500C (11), or This estimate does not take account of (a mean of 0.011 pc per 24 hours for well below the temperature of a burn the radiation dose arising from Pb" four subjects). On the other hand, ing cigarette. In addition, polonium absorption in smoke, either from the three smokers who smoked an average binds rapidly and strongly to surfaces, beta particles emitted by PbTM and of two packages of cigarettes a day and hence attaches readily to smoke Bi", or from the polonium daughter were found to have an average poloni particles. Finally, its intermediate half- which would arise in the lungs from um excretion of 0.065 pc per 24 hours, life of 138 days assures ample time for lead absorption. In addition, this cal a nearly sixfold difference. These re translocation of particles to the bronchi culation neglects the slowing effect of sults suggest that the polonium content to take place. smoke on ciliary action (17), which of the soft tissues of the body may be The basic question which arises from would prolong the exposure time and significantly elevated in smokers. our measurements concerns the radia increase the dose. For these reasons A comparison of death rates of lung tion dose to the bronchial epithelium we believe that this estimate is prob cancer in smokers may be made to the from Po" present in tobacco smoke. ably conservative, and the dose could well-known bronchial cancer incidence To put the following calculations in be 100 rem or more from this process. in miners exposed to radon daughters perspective, we estimate that the back The second condition defines the (IS). We calculate the lung-cancer ground dose to the bronchial epithe dose which might arise if local concen death rate in these miners to be 3 per lium is approximately 200 mrem per tration of polonium occurs in various cent per year; their radiation exposure year, dr about 5 rem per 25 years-- regions of the bronchial tree. The radi to the bronchial epithelium would be similar to estimates by Chamberlain and ation dose delivered by local concen about 20,000 rem in the 17-year in Dyson (12) and Shapiro (13). In this trations of polonium from particles in duction period (79). The radiation estimate we have used a relative bio the bronchial epithelium wall itself, dose necessary to account for the lung- logical effectiveness (RBE) of 10 for depends on the fraction of particles ac cancer death rate in males smoking 40 248 SCIENCE, VOL. MS DUP050312942 i. . ... i< cigarettes a day or more--about 0.205 ! percent per year (20)--would, on this I basis, be about 1300 rem over a 251I vear period. A dose of this magnitude troni polonium is probable only in I i localized areas of the bronchial tree, hut the causes of lung cancer may not he identical in the two cases (partic i I ularly in the Schneeberg miners whose i deaths occurred before cigarette smok ing was widespread) because of the presence of strong cocarciriogens in cigarette smoke (21). Because of the well-known synergistic action of ioniz ing radiation and cigarette-smoke ex tracts, or other chemical agents, in ex perimental cancer production (22), the presence of these chemical promoters might lead to cancer from radiation doses at least an order of magnitude less than the figure of 1300 rcm. A dose of 100 to 200 rem to the bron- .cbial epithelium may be highly sig nificant, therefore, and even doses at the lower estimate of 36 rem may not he negligible if the dose-response curve for cancer induction is linear for alpha- emitting substances. This general com parison is independent of the relative biological effectiveness chosen for alpha particles. We support the view that other chemical factors, particularly cocar cinogens, as well as physiological ef fects, such as alterations of ciliary ac I tivity by cigarette smoke, probably play an important part in the genesis of bronchial cancer in smokers. Our present conclusion is that Poa0 inhaled in cigarette smoke may act as an im i portant initiator in the production of bronchogenic carcinoma. Ed w ar d P. Ra d f o r d , Jr . 1 Vil ma R. Hu n t Department of Physiology, Kresge Center for Environmental Health, Harvard School of Public Health, Horton, Massachusetts i I1 References and Notes I I. J. Furth and E. Lorenz,, in Radiation Biology, A. Hollacnder, Ed. (McGraw-Hill, New York, 1954), vot. I, p. 1145. 2- F. W. Spiers and R D. Passey, Lancet 1953* U, 1259 (1953). 3. R. C. Turner and J. M. Radley, ibid. 1960- *. 1197 (I960). 4 F.. S. Harlow, Science 123, 226 (1956). 5. E. P. Radford, Jr., V. R. Hunt, D. Sherry, Radiation Res. 19, 29S (1963). 6. AP Prefiltcr, Milliporc Filter Corp., Bedford, Mass. 7- W, .T. Megaw and R. D. WlfTcu, Air Water Pollution 7, 501 (1963). A. C. Wilding, Nev Engl. J. Med. 254, 775 (1956). 9. C. R. Hill, Nature 187, 21t (I960), h). W. V. Mayncord, R. C. Turner, J. M. Rad ley, ibid,, p. 208. 11- K. \V ociuun. 4B,rtg1n97aH(, 19A6d2v)c.in, Inorg. Chcnu 2?ncJf- 1?- A. C. Chamberlain and E. D. Dyson, Brit. J. Radiol. 29, 317 (1956). 13. J. Shapiro, Arch. Environ. Health 14, 169 (1956). 14. Report of ICRP Committee II on Permissible Dose for Internal Radiation (1959), Health Phys. 3, I (1960). 15. C. W. Labclle and H. Brieger, Arch. Environ. Health 1, 423 (I960). 16. Dose calculated on the basis of retention of 3.3 X tO* pc of Po2, in 2S years, a volume of the bronchial epithelium of 3 ml, and a mean transit time of the nraens sheet of 36 hours. Tills figure is from analysis of human bronchial mucus flow by Dr. Bernard Alt shuler of New York University. We are in debted to Dr. Altshuler for making his cal culations available to us. 17. H. L. Falk, H. M. Tremer, P. Kotin, J. Natl. Cancer Inst. 23, 999 (1959). 18. H. Sikl, Acta, Vnio Intern. Contra Cancrum 6, 3366 (1950); S. Pcller, Human Biol. 11, 130 (1939). 19. A. Pirchan and H. Sikl, Am. J. Cancer 16, 681 (1932). 20. E. C. Hammond, `'Smoking In relation * to mortality and morbidity," paper read at the meeting of the American Medical Associa tion, Portland, Ore., 4 December 1963. 21. E. L. Wynder, Acta Med. Scatid. Suppl. 369, 63 (I960); F. J. C. Roe, M. H. Salaman, J. Cohen, Brit. S. Cancer 13, 623 (1959). 22. J. C. Mottram, Am. J. Cancer 32, 76 (1938); P. Shubik, A. R. Goldfnrb, A. C. Ritchie, H. Usco, Nature 111, 934 (1953); F. G. Bock and G.* E. Moore, J. Natl. Cancer lust. 22, 401 (1959). 23. Analytical work was done by Clement Nel son and Virginia Gilmore. Human lung tissue was obtained by John B. Little through the courtesy of J. Hallgrimsson of the Massa chusetts General Hospital. We are indebted to Jacob Shapiro and Robley D. Evans for valuable discussions. Supported by contract AT(3D-!)-3170 with the U.S. Atomic Energy Commission; the Higgins Fund, Harvard Uni versity; grant OH-00103-02 from the Division of Occupational Health, U.S. Public Health Service; and an Institutional grant from the Rockefeller Foundation. Initial work per formed while one of us (V.R.H.) was a scholar of the Radciiffe Institute for In dependent Study. 23 December 1963 B Novel Filter for Biological Materials Abstract. Thin plastic sieves with precisely controlled hole size and density can be made by irradiating plastic films with fission fragments and etching out the materia1 traversed by the fragments. These filters may be used for the nondestruc tive separation of cells of closely similar sizes. Studies of radiation-damage tracks in certain solids (/) have recently led to a method of drilling fine holes of ad justable size and number in thin sheets of these solids (2). The method has now been extended to a number of plastics which are commercially ob tainable in sheet form. From plastic film it is now possible to produce fairly large numbers of filters which have important advantages over conventional filters in certain research fields such as cytology and bacteriology. Briefly, the technique is to bom bard a plastic sheet at near normal incidence with fission fragments, which produce continuous trails of radiation-damaged material on the sheet. Fine holes are formed by pref erentially dissolving the damage trails in a suitable reagent, which then con tinues to enlarge the holes at a uni form rate until the desired size is reached. The number of holes is equal to the number of fission particles tra versing the plastic film (2). Only heavy, high-energy particles produce continuous trails of chemi cally altered material. Alpha particles from a Po!` source, although not suit able for most plastics, so alter the local structure of cellulose nitrate that holes form (Fig. 1). Lighter particles such as protons, electrons, x-rays, and y-rays do not produce this effect. Filters with hole sizes ranging from about I p or less up to about 10 p. and with about 2 percent open area have been made from 0.013 mm (1/2 mil) films of polycarbonate resins and poly ester resins. Filters have also been made from a number of experimental plastic films which are not yet com mercially available.. Extremely uniform holes are formed in polycarbonate film after irradiation and etching (sec cover photograph). Figure 2 is a graph of hole diameter plotted against etching time in NaOH solution for an 0.013 mm film. The rate of hole enlargement increases with stirring rate, reagent concentration, and temperature. Fig. 1. Holes in a cellulose nitrate film produced by bombardment with 3 Mev aparticlcs followed by a 3-minute etch in 6N NaOH aqueous solution at 75C. 17 JANUARY 1964 249 DU P050312943