Document qaQepdn9xRxkjpzkR7oXDxO7n

<0-9 <~s / ly-t,!]:;,,.; , nn*l ... * Otliiir:.` r-., inn Ey-li-rx l.|, ... i. 'h1 ^eiliriri-jr Tt itatiwiy tc The Mi-;.r - ratio (lr:#-rr .:i,. teniiitirti * < >g sugar- ti chromrijr:..- ~ . The n-vu!:. ita sh< w s. *!.. ighti ihftr I 2 glueo** tt-.a, an int<-r::----* of inverti**- - orinnl fit *. L The .eras I.a* `r- inchalit:^ N** rford '* lave bom <:----If!), Bar*. . (14). and U tors haw ? * ijaceJiaritl*** u-ing the hx" ' i honey m**-*-.* i he i-ii-nt:*"*- " as an actOi=e and . / tos*-* a:*J ydroi!i!'*r.' and ns of l'rn ! - ju-s that I" 'r' (,t he deter- ' i;iih\ It *cs a^ 1 I f many let ol' an * ' *' at fni'-te* " possesses invertase and utilizes sucrose in ; a'*?*.* Reference! ^ n1" T S. D., and Ededmjiv, j. Blochem. J., 48, 114 R. L, and Bcrso, D. J. Am. Chem. , V^TMTf- ,(1in9l5Aft). M.*/. Biol. Ghent., 160, 69 (1945). H. IM; 107, 15 (1934). J n. M. ibid., 195, 19 (1952). 4 Sox. N. /*., I53* -370 <1944). T SSr Biochem. Z., 180, 250 (1921). ' --1.1!BOLD, L. M. *i. Affr. Research, 35, 429 (1927). J Zyjrfc X. P. iWd., 35, 385 (1927). 2 mmocd, G. V. B. Ann. AppU Biol., 22, 301 (1935). ? O. J. Bxptt. Btol., 17, 18 (1940). e --UcSxM>( P. H., and Alson, ArcA. 5t'ocAm., 29, /mb, J. S. D., and Edelman, J. Ibid., 03, 467 (1950). _ i--eorr, S,, and Bacox, J, S. D. Arch. Biochem. and Bio*.T4i 476 (1952). J. TV., Ja., and Maher, J. /bid., 42, 360 (1953). - J. Ani. Chem. doc., 73, 1259 (1953). ' ^ ` received May 4, 1953. Egp2flt Tumors Resulting from fafeeddiug Plastics in Rodents1 JLi Oppenheimer, Enid T. Oppenheimer, Mir Purdy Stout, and l. Danishefsky / Center Research, if Pbyticians and Surgeons, University, New Yjrk City /ittfhro previous communicatioos {1, 2) we have ixriM various types of sarcomas which were intadls rats and mice by embedding certain plastic the anterior abdominal wall just venial to fefeta. The initial observations were made on rats mtbiAone kidney had been wrapped in cellophane Vfndoee hypertension. Seven of these rats, autopTttrftar nearly 2 yr, were found to have developed ^ms around the wrapped kidney. Later experiMfrsbowed -that subcutaneous embedding produced *4irjulta and the abdominal wall technique is ***ttsoral]y used by us. "'It^&tion to cellophane (regenerated cellulose) embedded a number of other plastics and ^ produced malignant tumors in a considerable Matage of the animals. These are all long-term ex*?**ta lasting usually 1-2 yr before the appear*JjjfJtalI, of a sarcoma. The final results of some . experiments cannot be reported as yet, since .****/ ^ses the time elapsed after embedding has sufficient for the appearance of tumors. TjJLtheless there are practical reasons for publish^4-rther results now, as plastics are being used ^**a^ more extensively on humans by surgeons j**|sjgical specialists. It is, however, very important -***tkt so far there is no proven instance in the .TTt?6 4 malignant tumor induced in man by 8 (Paraffinomas are foreign-body /t88! uot malignant growths.) On the other band, have reminded us that if it takes 1-2 yr . |wag supported by a grant from the National T^zJ*1**** U. S. Public Health Service. TABLE 1 Tumors Obtained by Embedding Plastics Subcutaneously Material Completed Experiments Animals Malignant tumors produced Cellophane A Cellophane A Cellophane A Cellophane B Polyethylene A Pure polyethylene Pure polyethylene Polyvinyl chloride Glass coverslip Rats Mice Mice (black) Rats Rats Rats Mice Rats Rats No. 15/52 8/35 1/22 20/44 10/80 7/38 3/29 17/44 1/50 % 35.7 22.8 45.4 12.5 18.4 10.3 38.6 Experiments Still in Progress Material Animals Malignant tumors produced Animals still alive Cellophane C Pure polyethylene perforated textile Silastic Tedon Nylon Dacron Dacron perforated Polystyrene Rats Rata Rats Rats Rats Rats Rats Rats Rats 11 1 1 12. 4 1* 3 1 2 16 30 31 3 15 21 29 30 22 for a malignant tumor to appear in a rodent, it may take 10-15 yr for a similar result in a human being. Malignant tumors, adjacent to or actually surround ing the film, have been produced in rats or mice or both with the following plastics: (1) commercial cel lophane film (regenerated cellulose), for convenience called by us Cellophane A; (2) the same cellophane film after it had been subjected to intensive extraction by methyl alcohol, called Cellophane B; (3) the same cellophane subjected first to alcohol and subsequently to benzene extraction, called Cellophane C; (4) poly; ethylene film, called Polyethylene A; (5) a pure poly ethylene film, specially prepared for these experi ments; (6) polyvinyl chloride film; (7) silastic, a silicone product; (8) Teflon film; (9) Dacron film; (10) polystyrene film; (11) with nylon film, so far only one tumor, & reticulum celL sarcoma surrounding the nylon, has appeai*ed, 441 days after insertion. Suc cessful transplantation of this tumor was made, pro ducing reticulum cell sarcomas to the second genera tion. The remaining rats embedded with nylon are still under observation.* To date the highest percentage of positive results (45.4%) was obtained by embedding cellophane B. Up to the present we have obtained a total of at least 126 primary tumors, including those from kidney wrap pings, and many successful transplantations. 3 Since the above was written 3 more sarcomas have appeared at the site of embedding nylon film. 20500001 BFG03678 kV At least 23 more substances (mostly other polymers or variants on those mentioned before) ore being tested for their carcinogenicity, but they have been embedded too recently for any report at this time. In addition to these plastics, we have similarly em bedded other materials as controls. Adequate controls are of the greatest interest and importance in such an investigation; and, at this point an addendum must be made to our previous report in 1952 (2). In that publication we stated that up to that time no tumors had appeared with the three substances embedded as controls; i.e., (a) the linters from which the Cello phane A was manufactured, (b) sterile surgical cot ton, and (c) chemically clean cover glasses. Recently, however, just before the completion of this last cover glass experiment, we obtained a solitary fibrosarcoma that surrounded a cover glass; this tumor appeared 659 days after the embedding, and was successfully transplanted. The cover glass was found broken into two fragments, but similar breaks were frequently found in the cover glasses that did not cause tumors. No certain explanation of this one exception among the controls can be made, but it is possible that some unknown carcinogen accidentally contaminated the cover glass at the time of the operation. In view of this single exception, a new series of control experi ments is under way. Subsequent to our publication, but independently, Druckrey (?) has induced sarcomas by similar pro cedures, using regenerated cellulose film and Polyamid film. He also produced peritoneal sarcomas by em bedding platelets of cellophane in the peritoneal cav ity of rats. Druckrey also observed that another rat, which had received cellophane orally, developed a lym phatic leukemia (lymphosarcoma) with malignant in filtration of the lymph nodes, liver, spleen, and lung. As this was the only such observation, we are specu lating as to whether or not the leukemia was perhaps spontaneous. The mechanism of production of these malignant sarcomas presents an interesting problem, and ex periments are in progress to try to find an explana tion. Types of tumors produced by embedding plastics are: (1) Malignant: fibrosarcoma (the great majority are of this type), rhabdomyosarcoma, liposarcoma, osteo genic sarcoma, reticulum-cell sarcoma, lymphosar coma, rhabdomyosarcoma (atypical), undifferentiated sarcoma, plasmocytoma, histiocytoma, myxoma, malig nant mesenchymoma. (2) Nonmalignant: 2 granulomas. Table 1 shows the tumors obtained by embedding various plastics under the skin, the rodent used, the number of malignant tumors produced and the respec tive percentages. Reference* 1. OfferHJCIMB8, B. 8., OrprwHtiMBH, E. T., and Stout, A. P. Proc. Bnc. Bxptl. BUtl. Med., 67, S3 <1048). 2. -----------. md., 70, 866 <1052). 3. DuvCKOSZ, H., and Schuahl, D. Z. ftutnrforech., 7b, 853 (1B52). Manuscript received May 10, 1953. 306 Volumetric Flasks and Microcell Filling Adapter for Use with the Perkin-Elmeri*-, Infrared Spectrophotometer1 O. D. Easterday,* F. Welden, R. M. FeathentqL J. P. Hummel, and E. Goldberg . Departments of Pharmacology, Biochemistry, and Urology, College of Medicine, State University of Iowa, Iowa City -y'ii. One of the problems encountered in quantitsfi^ handling a very few milligrams of material iai^ tion of a concentration great enough to penatfc preparation of good infrared absorption rtcoefe}* been solved to a great degree with the use oftie* paratus illustrated in Figs. 1 and 2. -- The 1-mm Perkin-Elmer microcell (Fig.il Teflon col lor Fixed . microcell needle- Syringe holder 0.25ml. ^ S> U-. ' ';:S O.f ml. Fiu. - 1 Tuken from a thesis submitted by O. D- Ea***^^. partinl fulfillment for the degree Doctor of work has been supported by grants from the 'Vm* Co., Cincinnati, and the American Cancer Society. * Fellow of the National Institute of Arthritis , olic Diseases, United States Public Health Service*' 2 0500QQ& W ^ * volt: to coi . ji of nee volu in tin . of a c _,, il'uvtrat . 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