Document vVJqBVGkvB7XJ1q78a9K47r2E

Journal for Cancer Research, Vol. 62, p* 564 !*g. >.0 \M35or (195b) From the laboratory (director; Prof. Dr, H*. Druckrey) of the Chirurgic University Clinic (Director: Prof* Dr. H. Krauss) Freiburg in Breisgau and of the Pathological Institute of*the University of B^nn (Director: Prof. Dr. K. Hamper!) - ( ^ Cancerogenous Effect of Ssbestos in Implantation in Rats'1* By Dietrich Schm2h! . . With 3 text illustrations (Received August 19, 1958) The causal connection between "asbestosis" and the appearance of lung cancer among humans is today considered to be proven (Lynch and Smith; Nordnann; ?/edler, Hueper, Weiss; Sohlig and Jabob)* According to Nordmam' about 20; of ail _ persons suffering from asbestosis later on have lung cancer. Hie latent period is` supposed to be about 15 to 20 years* . There j=-re .only few experimental efforts concerning any cancerogenous effect of asbestos. Uordmann ana borge in 1941 reported on experiments with mice which were exposed to as bestos dust. About 20/b of the animals suffered from lung cancer. In contrast to the positive result, tests of Hueper (1955) on rats, in vshich asbestos was implanted in the femur marrow, - were negative. None of the experimental animals developed a tumor. In the course of our investigations concerning cancer pro- -* The worA was made possible by the Uerman Research society. \ 2 duction by macro-molecular substances we have also investi gated asbestos. Below we shall briefly report on the results of these experiments which were begun in 1953* Methodology The experiments included a total of 39 rats of_both sexes from our pure stock 3D IV. At start of-the experiment they were about 100 days old. Pood consisted of a mixture of kitchen waste, fortified with vitamins, proteins, fats, and salts. Water was given ad libitum. The animals were observed until their spontaneous death. After thorough section there took place a histological examination in case of suspicious findings. .Ye implanted the asbestos in two different ways. One in volved pure asbestos fibres, like those used for filtering pur poses, and the other mineral asbestos. Initially the asbestos? fibers were loosened and cut to a length of 0.5 - 1 cm. In 21 rats 150 mg each of these asbestos fibers were implanted subcu taneously and intrapcritoneously. In the second experimental group mineral asb^st of the same dosage was implanted in 16 animals. This type of asbestos is fragile and it was implanted in small, long pieces of about 0.2 cm length. He suits Trie implantation was tolerated by the animals without acute damage. Only' in 2 cases there developed after the implanting of the asbestos fibers fistuals at the abdominal operation scar, but they healed-with sulfonamide powder treatment. The medium life expectancy of the anius.ls in the first series was 900 days and in the second 720 days. within the normal ranse. Thus it was roughly 3 22 months after the implantation of the fibrous asbestos there occurred in one rat a swelling which emanated .from the implantation located within the network. The histological examination produced a spindle cell sarcoma which was in some nreas mucuous, and forming fibers. At that time^ of the 21 animals bein used, lo were still alive. 5 additional ones among the group in the subsequent period developed malignant tumors, and in particular a fibro 111. 1. 21175. Subcutaneous grown spindl* gell sarcoma 27 months after the implan- uation of fibrous asbestos* . sarcoma, which had grown around the intraperional implantation, with metastases in the pericard and in the pleura, and further, a spindle cell sarcoma, emanating from the network, with metastases in the liver and spleen, in the kidnevs and axillary lymph glands, and finally 3 further spindle cell sarcomas which had arisen around the subcutaneous implantation (111. 1} and had not metastasized. In another rat 7/e observed in the stomach cavity a nucuous ribroma, which had grown together with the stomach wall. >,u i *5f SlilSi SV.v ' gsgpl;: 111 111. 2. Deposit oi1 mineral asbestos surrounded by a foreign body granulation tissue and swelling tissue. 2 - crumbly masses in central hollow space. A = smaller asbestos deposits in faorous binding tissue. G = foreign body granulation tissue. 1 = swelling tissue. . 5 The yield of malignant tumors thus amounts to 6 out of 17 animals. With 3 rats the swellings arose around the intra- peritonal implantation, and with the 3 others in the subcutis at the implantation point. It appears especially interesting that the sarcomas which had come about, had without exception metastasized-, but not the ones grcvm subcutaneously. The latent period up to the appearance of tumors, after implantation . amounted to 27-4 months, but It was so long that the swellings occurred only at an advanced age among the animals. .1 1. 3 Asbestos fibers enclosed!:: hyalineous binding tissue (A); it in turn surrounded by a granulation tissue (G) yjith penetrating tumor tissue (T) - o- V/e had similar results with a second experimental group, as in the case or the animals who had received an implant or mineral asbestos. The first swelling in this instance came already 15 months after implantation in the stomach area. This i was a case or a hemorrhagic tumor, probably emanating rrom the pancreas which had metastasized in the thymus and in the side kidneys. Histologically the swelling turned out to be a large-cell sarcoma. Among the 12 rats still living at this time, another 4 developed spindle cell sarcomas, which had all originated locally, anc. specifically with 2 animals around the intraperitcnal and with 2 animals around the subcutaneous implant. Here, too, the implanted asbestos could be proven in the tumor. The yield of 5 malignant tumors among Id sur viving rats is practically the same as in the experimental series with the asbesto.s. fibers, and equally the latent period of 21 - months. Frequently it was possible to prove the asbestos fibers in the midst of the tumor tissue. Histologically this provided in each 'instance faird'amentally the same picture, regardless whether it involved fiorous asbestos or mineral asbestos; in larger deposits one finds a central hollow space whicn is fi-Lled by crumb-like masses of ascestos (ill. 2 Z). The granulation tissue surrounding it encloses toward the periphery progressively smaller feci of asbestos (ill. 2 A), until in the end it involves only individualthread-like asbestos fibers wnich have been broken apart. In the farthest centrally located segments, the granulation tissue is poorer in vascular terms and richer in fibers (ill. 2 G). The asbestos fibers are then located in individual bundles in the low-core hyalinous binding tissue (ill. 3 A). Further toward the periphery, the granulation tissue becomes richer in cells (ill. 2, 30), and it also contains num erous multi-core giant cells around the asbestos fibers. Only outside this zone there begins then the area of the swelling-type cell growth (ill. 2, 3 T). . Discussion The results of the tests at hand show that in rats asbestos leads to the development of tumors after intraperitonal and subcutaneous implantation. This once again proves that a sub stance which produces cancer in humans also brings about the same effects in experiments with animals. The effect mechanism of cancer production of such implant ations is still unclear; In his investigations concerning the creation of tumors through foils of artificial substances and metals, Nothdurft came to the conclusion that it largely depends on the form and magnitude of the implanted material. Foils type implants produc-ed the largest yields, of tumors in his experiments, whereas the same material in the form of powder or fibers pro duced virtually no cancer. Probably in these cases the origin -of tumors can be based on an unspecific, mechanical effect of the implants, whereas their chemical nature appears not to play a determining role, insofar as the material cannot be meuaoolized within the organism, however, in some cases chenical effects may also come under consideration, for example with metals. In the meantime Druckrey, Hamperl, and Schmdhl were able to show thatafter intraperitonal- injection metallicemercury can likewise lead to sarcomas, although it is formless and is divided into small and very snail droplets, Thus the unspecific mechanical effect recedes in this instance. The present tests show that asbestos can cause cancer also when implanted in the form of fibers and snail crumbs. In the case of huraan asbestosis, lung cancer is caused even by the finest asbestos dust, which had also led to lung cancer in mice in the tests of Aordnann and Sorge. On the other hand, my own comparative tests, where other silicates, such as augite and tremolites, were implanted in the same form of small crumbs in rats, led to tumors in only a very few cases. Accordingly, the creation of tumors in these experi ments with asbestos cannot be based on a solely mechanical and thus unspecific effect, but appears to contain, after all, yet other factors. ' Also remarkable are' the purely local relationships between .asbestos and tumor, which allow the drawing of certain conclusion: about the hystogenesis of the tumor in~cuestion. Around the location of the maximum "concentration75 of the asbestos fibers, i.e. the center of the implantation, we only find a hyaline binding tissue capping, which evidently represents the remainders of the earliest reaction of the organism. Toward the periphery, where the asbestos has been blown apart into individual needles and threads, it is possible to prove a reaction rich in ceils, fresh or still under way, with a transition to sarcomatose swelling growth which is almost unnoticeable at marr.y points, V/e therefore believe we- are entitled to conclude that tne sarcoma development stems from this foreign body reaction, smoldering along abound the central focus. Summary Asbestos was tested for carcinogenic activity in the fora of fibers and small crumbs in 39 rats by subcutaneous and intraperitonal application, 11 of 30 rats which lived longer than 15 months, developed sarcomas at the site of the Implantation, cvnify thct the staff member who translated (he '-aoinq is thoroughly fomiliar with the n English longuoaes and that it is a true and :opiete translation of the cor/esponcin :ocument. s f/ ^F /Wa r ** 3 Language Service Bureau. !*t Dupont Circle Building Washington, D-C 20036 ; 'V- ii` i..c_-:.-%->=r.Ti'tc.' *.**..---*.".> -..?..*--*. "'% -CjSJ - ...r- ... . vrv--* -'*J. ,:L''rl ebri*t fur Krefosfurxi-huug. IU1. t>u,jGI-- 307 (lO.'K) . * - * -.; .v- va . . * '4-1 ^ deui Laboretorium : 1W. Dr. Tl. J>iu'cKi v) der Clumrgischen Uni* .^iudskiimk (Direktor: !>.*. Or. H. Khav:>j Freiburg u Dr. und Ucm Pnfholo* ' gischeu Institot der Univcivit.'it Borut (Direktor; Prof. Dr. H. Haju'ERl) ` ........ ujiccrogencWirkuug vonAsbcst boi IinplanlaUon an Batten* -- ;. - .' tVtOD - '. : Dietrich SchmAhl JCt 3 Testabbiidmigen ' (EiitQtguvqru am 75. Avyusl l'JSS) ' --- ----------- imgJt.piljjjV ' ' d'.'.Vcrj' - '* *>--"- .:T- ' -.'*- -V? ` ': . ^AV.'.'^' i 2;lA '* j _ -----Tr. wyxS, ~i.-^z*?fu"? ':*'?^T---~ *** .' '' ''7 - r - rs*&.: -rrv^ ^*^^'4v-_ Derknusalc Zusmmnicnhung zwischen ..Aslrcstose" und dem Auftrelen oa Lungcnkrebs ltoim Alcnscitcn gilt heutc ais erwiesen (Ly^ch und <->!jtjt; Nord^liot; Wedlrr; Hoeper; Weiss; Bohe:o und Jacob). <ach NOROJrA/ry b'-bommen .chra 20% Ilcr Jlonsrhcn, iiic an einer \.d>estose lciden, spiiUT Lungcnkrcbs. Die Lntenzzc*it soil efrvva 15 bis ?Jahre betrwgen. ExperimenteQc Arbcitco uber eine cancerogcnc Wlrkung ron Asboat agen our weuig vor. IsonmiAXX und Sonox beriebteten 194-1 uber V<Tsncbe an ilauson, flic Asl>oststnub ansuesetzt wornen wnren. Et^ra /% der Ticre erkmnkten an Luugcnkrcbs. Im Gegcnsatz zu dicsem r.-tlivt-n Ergebnis verlicfcn Dnterruuhtuig>n vou llUEPER (1955) an fciiii'-ti, denen Asbcst in dns Ecjnurmark injplnntjfrt worden war, negaiir. Keines der Yersuchstiere **nt^ckclte cincn Tumor- Wir baben im Yerlauf unse3*er UDtcrrucbnngcn uber die Krebscrzcu. rung durch makromolckulare Substanzen auch den Asbcst gepruft. Dbcr lie Ergebnisse dieser Y^raucbc, die 1953 begonnen -oTirdcn, soli im iolgenden kurz berichtct warden. Mcihodii Die Yennchc umJn&ten in*gramt 33 Bwtlm bciderld Gcschlmhta nnscrcs fteu*en SUmmn BD IT. Bei Versuch's^vyi00 'vren **e etw& 100 Tngr alt. Die Sahrung besttuid jm eincr Jt3*<ehk06t Ton KiichenftbfSIlen, die rait Vitumlnrn. ffotrinen, Tetten und Snlzen nngri-richcrt w-aren. Wasscr ^urar ad libitum ge* ^'cn. Die Tiere 'sroruro bis mm Sjontnnlod bcobachtet. TCnch jruncilicher ^ttfon erfo2gtc Ixri Terriachtigen Behtrxien eine histolngiache I'nioryuchting. Den Asbest hoben dr in zwin verscliierienm Fomwi imninntiert. Flnmoi fandcJte es aich am reine Asl>estfxcm. wir sir zn Filtcf7r?recken Tej-n-rndct vrrden, 'uvi rum ondrrun uro minerslUohen Abct. Dir Asbeetfaaern linden zuniiehPt ^igeloekcrt und an/ cine Lnngp ron 0,5--1 cn> gpsehnitteru 21 Batten nldellrn P" 150 mg diewr Asbcvtfnscrn milx*tcan und intraperiloneaJ iroplsntierL In der Die Ariicit wurnr Hnrvn die ,,Dc.it-.-lu- Fur- hitnf^grmein^haft" ermOgiieht. ? Krfl*ft.rvti. Kd. 62 28  . ^-^r..w.r---"*'"<-.^---.. ^S~-5. ^1 . iCgfzg:. :.' ~ IVi'*`^-1 560 E. Hlirb, W, LOjnwuad 0.2?eukbowtev. Slottwech.wl dor Tunreor>f^. Adrenocbrom hat ani' das. Wachstum. von Tran? lantationoitjTy^^ keinen Einflufl..!. E9 ist \rihrRchc!niicbT dafl mit/ ilfo-vor* ascorbbiiniiffllaatu^' Adrenalin su'Ad.roiioeliroin. oxjdi^rt wenieh kan^^ - .. , - N*** \ *0> . v glyrolyais. Adrcnoch'-om'h^ho.rnfli^ice' on the ;gro>nli'.;6f.'ijii^U`--:J tumours. It is.probable-ibat ailrecalin. con.he oadixad: to:;adrr>v^^. by-- means. of dehydrouRcorblc- acidifyr' . ..-. :i'.-, ... .' ;!V:V'jfe]i.',jf \ '..V.'V*. .^-.'c !.\ T^*-' y-\A' iitcratur ;;/';-V" - .":.^V Gsxkh, D. E., and F. G.Ogstom The mechanism of the'reficiaoh-iBa-4sT--with molecular oxygen J/LL Biochem. J. S3,19$3 (1035); 30,620 (1936). -- Hajrj^r? SIasok, J.: The cHmiatry of a'drenochrome.-nd'.rts derivative*!." J;' rhcraJ-tv. 1950, 2, 1276--12S2. ---Hi3SR;E., W. LQbbs-u, 0. XECBSOETTtR:. t/Wr-X* Ein/luO ron Deh^droaecorbmsaure: an/ den TiimorFtnffwcehsd. Z. KnOx^a*-* 1058 (im Dmck). -- TCrsm. B.- (1) Die Autokatalrne dcr Adrian1ir*>.<; Biocbem. Z. 220, S4, 92 (1930). -- (2) Die Omegakatalyse dor oxjdatin-n rhV y.r? apaltnng; Biochem. Z. 25C, 330 (1931). -- LzttbA, PL, P. HARqujam ii. L i*.^: Weitore Unt->~ uchnngen fiber die xeiiteilangsbemiuendo WIrknng rob M1?-;.-* und Derivnt'"i. Hoppe*Seyler Z.' physiol. Chem. 231, 99--103 (1952). -- suae, 0.: ttber deiT Stoffwechael der Tunioron. Berlin 1926. '>rp{, Dr. W.u.tftr Luttbs, Bentsclio Aiadomie der Wisseaf-cbtffva, Gesehwcdstklimk, Beriio-Baeh,,.,.- ' G2 Dimucjx Schm-Ilbl: rtrcitrn VemjdwgnjpiK* crhieltcn 18 Tlere den znmeralisrhrn Asbnsi. in rlcr sieichqq Dosis ringcpfUnzt. Phfe Form ries Asbestos i*t- briichig uwl wnnic in klohuin, lan*. lichen Brocken Ton d-.viv 0,2cm I/uigeiioplimtiort. ; . ` .V. ' jr ' ^ T,` Die Implantationen warden,yon deii Ticren olme akute Schmligun^ rertrngen. Ledigiich in-2 Fallon entwickeiten sich nneh tier Einpfluh'- ' : ' "' xiing dor AsbcHtfafcoru'ji.', dec abdomiueSen'., itionsnarbe, die ttb^- Sulfonnmid-Pudcr- Behandlung auslieiltea'- Die mitt.lore Lebenserwiif. der Tier* betrug In ersten Serie 000 Tag- 720 Tiige in der zwc:- .Sie lag demit ctw Bercicb d*r Norm.-' .. --* - - 22 MonaU ..<* 4* Tmplantntiondesfaaerfor- migen Aabestes entstnud bei einer Ratte eiue Gv- sehnrulaf. die von dem im Net-7, liegenden Iraplantai ausging. Die ^istolngisclir Untersucbung orgab fin stoilemreiso vcrscnicuarn* des; foserbildendes Spin* I. * r ML... '** dclzellsarkom. Za dieeeffl Zcitpunkt lebten von <irn Alil>, 1. 2117<?. SubeniAO sre'rchscs Sjiiiirtcbeilmr* Aebtflkom 27 Monnte naeh ImplimtnOun twj foeerf&nnttfem 21 eingesetzten Ticrefl noch 16. 5 we.itere vor. ihnen enrnickeilcn in ucf FoJge2i*it noch bosartige Tumoren, unri*zwar cine Fibrosnrkom, das u lias intrnperitoncnle Impiantat gcwachsen war, mit Metastasen im Pmhard and der Pleura, ferner cin SpindeJzellsarkom, vom Netz ausi^uemL mit Mctastascn in dor Leber und Mite, in den Nie.ren nmi Axiiinriymp0- druson und seblieClich 3 weitere Spindelzedsarkomc, die am (ins'*'"" evtanr Impiantat hcrurn ent-standen waren (Abb. 1) und nicht mc-ta>ta* siert batten. Bei ciner weitcron Ratte beobac-hteten wir noeii in de< BanehhohJe eiu verxchUumendes Fibrom, dns mit der Bauch wn*,a *** Wiu-hseu war. ... '-. -' ^^'~-^^'.'.Ti.'-jSi:'~^.-. - - - - r.~.s. * ..- --.-.^> -"X-: '-V.. z*&s*&wt*&? : ,-^ri^v?ci;:^-r?-ia^i5a *" **y~r jjj-. pnftrt&t" * : ~*-r?:<t^k-^f$~T->Z - -. ;-> *'> Vti.<rz^^i'-i'>';pJ* Dio AusbeuU* an malignen Tnnu.ivn Ix-trn^l ib-mnnch 0 von 17 Ticren. jjei 3 flatten ent?tmden dio CJ*.<b- -'Me mu das inlraperitoneale Im- ; ^T-v %^p,jS\ '; ` r*. i.1*-' " ' Jl- ;v. ?5-. ,w,.- ._ ,- . * , ______ .. Ah*>. 2. DcfoC nummllMchon A>l>ct*8. umgrbcu vn cinrm >'jTii<ilkorrrjrKoula i<.tjypr<rcbe Wirt (Joscl)*ruJytCTWtl>e. Z hrockJiir* Mnw^n !m zontmlfm flohlmam. J iUeiurre A*>^(- dajxits In fibrOarm Blmlnrcivche. Q FrrnirifcorpercTuuttiatioasKCweijo. T (lescbn ulMK^^elxj ptantat herum, bei den 3 nndercn in dr>r Subcutis an Her Impiantafions^cUe. Es erscheint bcsomlcrs inl<Tpysant, da2 die intmperitonenl 3?' 5* * I 564 District ScnxiXaz.;.-:- ent.-dandenen Sarkome auso-.iiolsios nit-tn y!n*icrt batten, die: subcaf"^ Ahf.. .1 in hvhinu^n BlD<lr.rwebe e!ncrtcti)<*wei {A). diM uiiiKrbcs ** oiiiom (xmiialnt lotisscrwrho 7) mit eindrinecndeis Tunirjfcwefr (D. . Ein ahnliciies Ergebnis erhielten wir in der ztreiten Versnciisgruppe- ala bei den Ticrcn, die den mincralisehen Asbest impJantiert befcommen batten. Pie erste Gcsehwidst entstaud bier bcreits 1"> Monote nacb <Jff Implantation im Bmicbmum. Es handeltc sicb uro einen, waiirsc.Vtn- lidi rom Pankvcas anegehendcn, hamorrhagischeu Tumor,. tier in `k* Thymus und in die Nebenniercn metestasiert hatte. Hlstologisch er* 'vie? sicb die Goschu-uist als ein grofizeltiges Sarkom. Von den it* diesr^ Zeifpunkt noch Icbenden 12 Ratten entviekelten nodi 4 writer? >i,lp' ft zcllsarkomc, die sauitlich loknl entstnndcn waren, uno zwar i*i - * uiq das intmperitojicale und hoi 2T3cren nm das sulicutane lui[ a , / * ' Cancerogcne Wirkung von Astast bei Imp; . i.'.livii an Rotten * VV */ 565 , ^crltni. Audi hir konnte Vr imp^ntiri * st im Tutnor naohge- ^csC1i werdcu. 3)ie Atislieui*' von ; i.-iuoron dntcr 15 uber- lebenden Ratten ist prukliV'ii die yfotoho u*f.j in <W Versachsserie-mit j^bestfasenii ebenso din Lutenzzoil -ml, 21 m 4 Monateri:* *' ` ; HSulig gei&ng es, die Ashest-lb -:iu iumitten ron Tumorgewebe n^ciizuircisen. lllstoiogisch-ergab rich dabei immw grmids&tzlich dasj^jbe BUd, gleicligOltig, ob es sich um fascrigen Asbcst oder mineral!jehen Aabcgt .handelte: in groBereu Depots findet sicli ein zen(mler ilijlilnuny det von brockligcn Asbcstmassen crffdlt ist (Abb. 2 Z). Bos ihn umgebende Granulationsgcwebe schlieBt gegen die Peripherie zu tanner. kleiner verdende Herde von Avnest ein (Abb. 2 A), bis es sich jcIiIieSIicli.nurmehp tim eiazelne, ausdnnndergesprcngte faden/onnige Asbestfasero handelt. In den am weitesten zentral gdegonen Abschnitten ist das Grannln tionsgewebe gcfaBarmer und fnseiTcicher (Abb. 2 G). Die Asbestfnsern liegen dann in einzclnen Buscboln in kernarnu'm kyalinem Bindegewebc eingebettet (Abb. 3 A). Writer gvgen die Prripbcrie zu Trinl das Granulationsgewebe zellreicber (Abb. 2, 5 G), entimK aucb einzelne vielkernige Riescnzellen tun die Asbestfasem. Erst auBcrbalb dieser Zone beginnt dann das Gebiet der gesehmiIstmnBigen Zellwuche.*>*2 (Ah'b, 2. 3 T). . Disht**ion ' Die Ergebnissc der voriiegenden Untersucbungen zeigen, daB Asbest bei dor Ratt-e nach intmperitoneaier und subeutaner Implantation zur Entwicklnng von Tumoren luhrt. Dandt ergibt rich erneut, daB eine Substanz, die btim Menscbeu Krebs erzeugt, aucb im Experiment am Tier die gleichen Wirkungcn horvorruft. ^TV^ncrsTTipclianismus der Krcbserzcugung soicber Implantate ist noch nnkiar. Nothdubft kam bei seinen Untersuchungen uuer ur Erzcugung von Tumoren dureb Folien von Kunststofen und Mctallen zu dcra SchiuB. daB sie U'eitgehend von der Form und GroBe dcs impiantierten Materials abhangt. Folienformige Lnplantate ergnben bei semen Versucben die groBten Turoorausbcuten, u-abrend das gleiche Material in Form von Pulver oder Fasern praktisch keinen Krebs er?.engte. In diesen Fallen kann die Entstcbung von Tumoren vahrscheinlich aui einer unspezifischen, mechanischen WIrkung der Impiantate beruhen, wahrend ihre eiicmische Natur keine maBgebJicbe RoUe zv spielen sebeint, so/era das Material im Orgonismus oiebt abgebaat trerden kann. Es kommen aberin maneben Fallen aucb chemische ^Firkungen in Frogc, z. B. bei MetaUen. DarcSBET, Hj-MTEBl nnd ^citmahl konnten inzwischen 7.-. .daB metallisches Quocksilber nach uitraperitonealer Injektion cK*i. falls zu Sarkomen fuhrt, obwohl es formic* ist und in kieine und kloinsie TVopfchen verteilt wird. Hicr 7,. XrrMfonch. Bel. C.i !V :=J / ....T -:1?" , --- - . - 'v". ..~~.::u* 566 Dietrich Scjimahi.; *w,r. . ' '** ': tritt also die onspczifische mcchonische Wirkung zuruck. Dto ^ . Begendcn Untersoohungen zeigen nnnj dw/3 Asbesfc, awh in Form y^- Fasem imd'klcinen.; Brocken unplantieif, Krebs auslpsen feanjj. LungcnUrefcS;.bet der nKmchHchen.'Afibt^tiisc wild,sogai (lurch Asbcststaub. ausjrMosV'der 'aueh' 'an_ (ler ilaus'in' den.' ^crsudiorTb"^ NpRD^U'tK und SoROK zu lAtngenkrebfl gefulirt batte.iAbi' dor * Scito habeii- eigeh^ yprgld,clisvem:c}ie, hi dcnca ^dp^i..?iiik,\^.:v^ z. B. Augifc and Tremolit,: in. der gldcbon.VForm'Tbn klohvjn BrkHv an Rattan implantiert '^^den>..cor m gani wcnigen-Fsncn zTr.Tati;-^' gefuhrt/. Demnach: kann^die' Rrzcujjjing von Tumoren- iir diesch YrS' suchen mit.Asbest nicb'f-;'au{ 'fdner-'bioB raecbanischcn'ln'id d: bxr't-j' spezifiscbeti Wirkung'.bifritheii, sondem -`v-ltemt. d<\.'b . boch'^tndrre toron zu entbalfcen;' : - :.v " !7,''(%Vv: : Beracrkenswert sind such die- rein ortlicheu Beriehungen zirird^t," Asbesfc und Tiunor, aus denen sich gewisse. RuckschlusaeLa'oi.die genese des joweiligen Tumors ableiten lasecn.. Um den'Orf clef gn;^, ,,Kan2enfcration`4'derAsl>cstfasern, also umdas Zentnun den iniplnatrirf-j. sfinden wir nur cine hyaline bindcgeweUigc Abkapselung.'dio olfreV* die Rest der fruhesten Reaktion des Organismus darstellf. Kach >% Peripherie ru, dort, wo der Asbest in Vereinzelte Kadelnvnnd.i?S'_'i auseinandergesprenct 1st, laBt sich eine zeilreicbe, friscHe haw. nod; h- Gang befindlicho Reaktion nnchweisen, die an vielcn Stellcni-vn "j- merklieh in das sarkomatose Geschwnlatwachsfcum - ubergebt. .A\V gb*ul>on deshalb, zn dem SchluB lierechtigt zu sein, d&G die S*rk'r5 entwioklnng aus dieser nm den zentralen Herd fortschweiendon FremJ- korp rrraktion hervorgeht. ' .' Zu-wmmznfassung Asbest wurde in Form von Fasem und kleinen Brocken an 39 bei subcutaner und intraperitonealer Applikation au krebserzeuger^D Wirkung gepruft. 11 von 30 Ratten, die linger als 15 Monare entwickelten lokal an den Implanlationsstellen Sarkome. . Summary ' Asbestos was tested for carcinogenic activity in form of fibre* *-`% small crumbs in 39 rats by subcutaneous and intraperitonecvl arP1' cation. 11 of 30 rats, which lived longer than 15 months, ders-'^* sarcomas at the site of the implantation. . Litcratur _ Bonur.. H., . C5. Jacob: Nenere Gedchtspunkte tiber (ten i^inpcnUrv* ^i>x Kft**'Asbestarbeiler. l>*ch. med.. Wseiir. J95fi, 231.*-- DRCCKRrT.^ H- H- -!>x* o. D. ScmtAnr.; Canccrozenc Wirkune von meta!Ii*cbera Queeksilbvr. . \ ' w- ..-. -*v ;%.* x*'-";.;.-"t-ifr^: ~ ' -tr ;jk . -- . .*--.v? - ''?$. . .r; ' :iii##. ' *,,. A^-.V.3fc*-*. *#***^**;. .*'*> ; - '&,!:*& :* ** n -.i . ' Ganccrogcue Wirkung vim Attest boi f'.itpl.MiU'fion tin Ratten 567 . ""V-i*.^ v -c>*.<*>*-. ;--'^.y..^v:^kir^.- _' -- -- . iu. ^JL . . ;.* ' ' ' ^r ri;-'-. ?-w?> E! ^ tfj'ViSI ._,.. Jv^rz^fteri, --- -- - -- - - -- - MaiijimJf-.-^ t^^t>Yn4gAr3**3k?* - -T-7 . -.,'/-A _ ' ":~U'-.:nVr..i^-'-t.i-- ' 'X.-~**tft .4St^-: .1 Id Lr"*V Si -. <^S . .j,. PJ, 511 (1957). -- ITtrL7*KK, *'' ('.: !?'' ->t developments in environmental Arcb. Patti. (('liicuno) *'\ 3r.o, ',-'< (Kl'-t). -- Experimental ptudics in carcinogwiesi*. J. >'.(. f'- i''cr Just. I**. U3 (1955). --Ltsch, K. M. and ^ jV. 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