Document 4vLwxK46MmBXm27V3w1RaE1Q

anil .... 'Oelllnr;i- [yilro. hi, ... t aid "hit Sawllar:.:>- n. itutiwly !<. ;.v The Miu.-.r !i Ba (i >) i.. ratio d. vr-: teriiiiia-ii >.. ng sugar- l . ehromo.T;.-r .. . The n--u'.:i >*, ita show z. ' iglit; I 2 gluco-e eea. ; an intiT:-.--of inveruw . ormal fii ,. -1. The |.r--. .eras ha- `e. includim; . rfoid lave been i;<~ > 12), Bais.r, [14), and Wvi. tors lu'f'-* "* isacvliarides t irilig tin- iv'"- i honey i he identi'-'s as an lctose ami - tosc and ydrOrhl'T.' >,e ami ns of i ra.-i * ,,,> that `,Ot he lie'.*-:- " ' side. It scs a> a f many " u-t of a"11"" at ............... VP system Reference* - T s, D., and Bdelman, j. Biochem. J., 48, 114 } 't*' 'amrrtxs. R- f*., and Bcrso, D. F. J. Am. Chem. Sue., S M950) M. /. Biol Chem., 160, 69 <1943). B. IM., 107, 15 (1934). J S&L M- IM- 19S- 19 (1952>- X. nut., 153, .375 (1944). * *2* E. Biochem. Z., 180, 250 (1921). 'mui, L. M. J. Aar. Research, ZS. 429 (1927). * E. F. nut., 35, 385 (1927), 4 nirr-- G. V. B. Ann. Appt Biol., 23, 301 (1935). t **"s O. J- Exftl- Bil' 17, 18 (1940). 5 I^jchatd, P. H., and Albon, N. Arch. Biochem., 29, SB IJ930). J, S. D., and Edelman, J. Ibid., 23, 467 (1950). * i^w'itt S., and Baco.v, J. S. D. Arch, Biochem. and Bio478 (1952). J. W, J*.. and Maher, J. Ibid., 42, 360 (1953). - J. Am. Chem. See., 73, 1259 (1953). : ncelTed May 4, 1953. j6jpant Tumors Resulting from libeddiog Plastics in Rodents1 flOppenhrimer, Enid T. Oppenheimer, 1dm Purdy Stout, and (. Danishefsky nJiintitl Center Research, / Physicians end Surgeons, RhmUt University, New Y irk City .u--'lfUiyffctftMfNbfl,wa - 'll"hro previous communications (1, 2) we have ifcsnM various types of sarcomas which were in- #Miis rats and mice by embedding certain plastic te la the anterior abdominal wall just ventral to IdSaoa. The initial observations were made on rats *Uh one kidney had been wrapped in cellophane ttfndace hypertension. Seven of these rats, autop- Ai after nearly 2 yr, were found to have developed around the wrapped kidney. Later experi- *** showed that subcutaneous embedding produced W^BjTesults and the abdominal wall technique is Mtftamily used by us. addition to cellophane (regenerated cellulose) -** "55 onbedded a number of other plastics and Induced malignant tumors in a considerable WsaUge of the animals. These are all long-term ex- ****& lasting usually 1-2 yr before the appear- all, of a sarcoma. The final results of some axperiroents cannot be -reported as yet, since rases the time elapsed after embedding has "*^ra sufficient for the appearance of tumors. "ulheless there are practical reasons for publishXAsther results now, as plastics are being used 2TMd more extensively on humans by surgeons ******?cal specialists. It is, however, very important fi*at so far there is no proven instance in the of a malignant tumor induced in man by "*~nl8 a plastic. (Paraffinomas are foreign-body ut malignant growths.) On the other hand, T*Hpsts have reminded us that if it takes 1-2 yr " 2"'' Wfts supported by a grant from the National TESrtNwe, n. S. Public Health Service. 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 Rata Mice Mice (black) Rats Rats Rats Mice Rats Rats No. 15/V2 8/35 1/22 20/44 10/30 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 Malignant Animals tumors produced Cellophane C Pure polyethylene perforated textile Silastic Teflon Nylon Dacron Dacron perforated Polystyrene Rats Rats Rats Rats Rats Rata Rats Rats Rats 11 1 1 12 4 1* 3 1 2 Animals still aKve 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; (0) 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, a reticulum celL sarcoma surrounding the nylon, has appeared, 441 days after insertion. Suc cessful transplantation of this tmnor was made, pro ducing reticulum cell sarcomas to the second genera tion. The remaining rate 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. Since the above was written 3 more sarcomas have ap- ____.1 .A At,, alia a# amhail^lni* MvIaii film o w o. o At least 23 more substances (mostly other polymers or variants on those mentioned before) are 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 (3) 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;ion. Types of tumors produced by embedding plastics ire: (1) Malignant: fibrosarcoma (the great majority are }f this type), rhabdomyosarcoma, liposarcoma, osteo genic sarcoma, reticulum-cell sarcoma, lymphosar:oma, rhabdomyosarcoma (atypical), undifferentiated sarcoma, plasmocytoma, histiocytoma, myxoma, maliglant mesenchymoma. (2) Nonmalignant: 2 granulomas. Table 1 shows the tumors obtained by embedding various plastics under the skin, the rodent used, the lumber of malignant tumors produced and the respecive percentages. leterence* .. UPFBNHKtMBs, B. 8., OrPBMBcniBR. E. T,, and Stout, A. P. Proe. So*. Baptl. Biol, lie<., 67, 38 (1948). :.------- . nu,, 79, see <ma). Duuckiuct, H,, and SCHltanL, D. Z. Naturjorsch., 7b, 353 (1652). lanuecript received May 19, 1953. Volumetric Flasks and Microcell Fillip .; Adapter for Use with the Perkin-Elmeri* ` Infrared Spectrophotometer1 . W3 O. D. Easterday,* F. Welden, R. M. Feathery- J. P. Hummel, and E. Goldberg ^^ Departments of Pharmacology, Biochemistry, and Urology, College of Medicine, State University of Iowa, Iowa City One of the problems encountered in quandtij^ handling a very few milligrams of material in j,| tion of a concentration great enough to peiag|, preparation of good infrared absorption record* fc, been solved to a great degree with the use oftfe* paratus illustrated in Figs. 1 and 2. . The 1-mm Perkin-Elmer microcell (Fig^J'i 1 Taken from a thesle submitted by O. D. -- lartial fulfillment for the degree Doctor of ?ork has been supported by grants from the ft. Jo., Cincinnati, and the American Cancer Society. * Fellow of the National Inetitute of Arthritii ilic Diseases, United States Public Health Serwe-^gg* 0500002; 2 VOIU .v in tin . of a c _, lllustrat , ,-oiwtriet. ,:!v large .the no. of the s r the fing n and Si xi Urchin: ru urchin y -tccl S-in. thiornia. T : Cotnpan; r\b!(>m to t uitory. 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