Document 8296agwLY56YobD6vVBY51VMd

JAN 3 0 1973 Polychlorinated Urphcji^Rnd TriphcnyMnduced previously unrcpotled Ic&ton, K per* Gastric Mticosal Hyperplasia in Primates plasia and dysplasia of ihe |iuric mucosa, occurred in alt animats that Abstract Polychlorinated biphenyl or iriphtnyl ingestion by subhuman primates tor 3 months produced hyperplasia and dysplasia of the gastric nutccsa. The con centration of the biphenyl within the experimental diet was less than an order were fed diets containing the chlorin ated biphenyls and iriphenyls (I'CTt). Male rhesus monkcis ranging in a;e frons | i/J to ' years and having an of magnitude t'enter than that occurring in random food sat tpies sold in the United Stales and less thnn levels which have occurred in food prsducts as a result of industrial accidents. The increased eellnlarity, abnormal t l1plastic growth pattern, antI invasion of the adfaecnt tissue region indicate com/ ronustd gastric average weight of 2.9 kg were u,ed m this study. Sin animals "ere f.-d a diet containing 300 parts of PC ff ( Vroclor 1248) per million ar. t ,,x were enen function and are sugg, stive of an eventual neoplastic Iransfortnction, 5000 parts of PCT (Aroclor 5460) per million in the diet, for 3 months The Polychlorinated biphenyls (1'CB's) peeia. edema, and -eueform lesions remaining three animals served as con have been widely used in industry for and hepatic alterations including organ trols- During Ihe course of the experi over 40 years is sealants, heal transfer hypertrophy and proliferation of the ment the animals were given access lo agents, plastlcircrs, adhesives. and dielcc- endoplasmic reticulum were observed in 400 f of the experimental diet daily. UiV fluids in capacitors and transform* the subhuman primate. In addition, a T1c min;al> co-dimicd to r:-.t iiwougr- eri. Global environmentaf entunmina- put the experimental period, j.'ihnuch lion (/) and their presence within the there was a decrease in bed) weight of food chain have occurred through in approximately 15 percent in b.vh of the dustrial accidents and improper dis experimental groups. Within ] month, posal and misutrs of the compounds all of the PCD-fcd animals, and within (7, 3). I'ol)chlorinated biphenyls were 6 weeks, the I'Cl -fcd animals, haj hatr reps'tted In the United States in coho loss from the head, neck, and bice. A salmon in 1909 and then in nulk fat progressive, generalised, -irhcuiancoui (2(1 parts per million), poultry and eggs edema, particularly of the face, was (4.1 ppm), fish <35 ppm), and cereals manifested as swollen cjel'J. ar.d lips. (less than I ppm) (2). The food and A purulent discharge exuded from ihe llruj; Administration is presently re , eyes, and ivolated aeneform le.ions movin'; frtult the market known Con were present on skin areas de'OiJ of taminated food samples which exceed hair. User hypertrophy '2.* pei-Viii r-r 5 pp<`.t- However, as a result of occult the body vs eight in controls. 4.5 per environmental anti food exposure, cent in the DC 11 group; 5 6 percent in significant levels of ('CD's (over t ppm the I'CT group) was attributed mj-niie in adipose fi-vuc) arc present in over 30 to a proliferation nf the smooth endo- percent of random samples taken from plavmie rctrcttluin olrsciecJ e'e.-tron the (metal population of this country nvieroscopieally. I'.JenuU-us ihiel.cnni; (d). Two separate, well-doc unsettled in of the siomnch wall and niatked hsper. dustrial accidents resulted in high con trophy of the pyloric and fundic satiric cern rations of I'CBs in rice oil (2000 to mucosa occurred. 3000 ppm), whi.'h was subsequently I he hyperttophic gastric mucosa sv.vs consumed by over 1000 people (3), several limes thicker than the enuirel and its fish meal 114 to 30 ppm) ued ntucosa and was composed of greatly for poultry feed (.'). T)tc effects of elongated hyperplastic glands ton:.lin J'C H s on humans include aeneform ing mucus.secreting cells (Tig. I). The skin eruptions, pigmentation of nails cells containing brsdar posiiisnicsl and skin, .eye discharge, generalised nuclei, aliund.xnl slightly acidophilic swelling, weakness, vomiting, diarrhea, cytoplasm, large vacuoles. and a micro- weight lots, and fetal toxicity (J). Addi. vtlluus border abutted on a basal lanuna. (tonal effects observed in expcrinscntal I'levention of discharge of the secre minis1* fed the compounds include tion owing to the depth and apposition hepatic posphyria in chickens and rab bin (fi). prolifetatiun of hepatic smooth endoplasmic reticulum in rats (7), mice, and monkeys I A), increase in Cirt-tin licpatic rnryme activities in rats (7) and kestrels [9), nctwopathy in rats OO). lymphopenia and immunn-.iippresnon in rahbits and guinea pigs (6), and estrogenic acnvily in the rat u'-enis fll). In the study reported here dcr- Tig. I. (A) Normal ryloric rl.iods ol ih; fast lit msicnsa I.U) are scpai.-ted fri r i Ihe snhmireos.a IS) t-y she nrvcl-rrx mueo.ae ti). (Ml l oliov-r.ip re'.'J nated biph-nyl ingeshcin the hypc-it'1 'c iiiucos.it plan.Is pen.-ir.ite the uii.ci I ruirensiw to fnim rm-ei- 'ii'.ed cv.M cl ix, subiirnet*sa. Celli Jininfi cyxt sim- -r 'o area indicated by arrow (-) 's.Jh-V"11 u fied in' Fig. J. I *40; seila-ra-pgrttrtTr^f'P talplog<^Alterations including alo ws HONS 20S547 of Ihe (lands predisposed to I he devel fTl-O.. opment of targe mucous cysls. Glands v.............. ^ of the funilic area which normally con tain variety of secretory cell types X^ ; *4 consisted primarily of mucus-secreting cells. - Widespread pcnclralion of the mul- cnlaris mucosae and invasion of (he r ^w ; * ,. Vfl-w.* \- 'v,`v. : <.* ,i '.? *A . %* *'*a*r * *U submneosa by ihe mucosal epithelium (Kg. I) was observed in (lie stomach uf each experimental animal, l.ar(c cystic areas filled with mucus and lined with elongated mucus-secreting epithelial cells predominated in the sub mucosa, Other ceils assumed a glandu lar pattern. Serial sections of the sub mucosal cysts demonstrated stratified arrangements or proliferating epithelial cells xvhich penetrated the basal lamina and invaded the surrounding cnnnccitvc tissue of the subnmeosa f[;i(. 1), I'piihclial origin of the stratified ceils was determined by rite presence of nucleoli and similarity of site nuclei in sire and shape to the nuclei nf llte epithelial * r *. * r. * >' .- *: ' r _fXc .1 I`p*i, . m * ** ^ <V . T 4 .-, *.';, . * , ZX V;^ A j 'j*:4: k'1 v ,<w * r' Z**5 * ' * t .** . .yv.'* .a--r ,V -* VI *' V ft 4,-ci -,,,- `. .,r-. J '*-* i* , t , *> t-.v -.`T1.* t- 1. -- . '.T-.V* _>| ' ` V. ,. ' 'A ' ' -i > Yjj y;Z$ ;^ \ :' 7 ilv- i ;' - ' V-: V: h 'A^. . * y -y- t f.,`A.^r aU kWl Af< . J^jal t* ,1 J #- ---'------| ,--,k * ^rt*. ^| . A cells Imins the cyait. Occasionally, iftcgnlar hypcrchromtc nuclei and pleo morphic evils vv ills nuloiic figures were present in the cells of the sitaitficd areas. The presence of inflammatory cells in llte suhmuros-1 in proximity ro Tip. 1. Glandular epithelial cells that have extended tmm Hie mueosx into the sub mucosa cncompasi laipe cysts (C). In some Altai (-*) I he ertihclt.il cells air stratified and pencitiilc inlo the connective litiue of the stthmuen-.a, `the cell nuclei of the nt.ititini arm li similar m lire and appearance lo Ihjl ol ilie liinplj colnmnr epithelium tltai lines llte temainder of Ihe c>st (ser inset). Scii.d senium of the fi-ure conliimcd ihe stratified arrangi'iuciil of the epiilicliat celli (x250, ir.scl xOJO; stale represent* JO pin). . I Ilic glandular and cystic clsati(cs was common. llte increased ccllul.irity of llte monkeys and Human patients exposed dysplasia of the gastric mucosa of sub mucous glands with invasion of the to the rCU'i may be related ts> gastri human primates necessitates clarifica nmsculatis mucosae and accruv.p.'inying tis, Replacement of the parietal cells by tion of the carcinogenic polenii.ils of inflammation noted above it Imlologi* the niucus-tecrciing cells which oc tltcsr compounds, I rally dctcrihcd as a hypertrophic curred in the fundic glands of the J, R. At LtN gastritis, 'flic extemion of Ihe inucos.il more severely alTectcd animals may re D, ft. KonnxCK cptlhclial cells into the tithmucosa and sult in achlorhydria and cvcntirj Dtpanmfnt of Pathology, finiteat Ihe pretence of irregular tlrarifieJ ar- pernicious anemia owing lo the lack School, and Kcgxonal 1`riir.tnc Rnsurch, fatif.emcnis of epithelial cells within the of intrinsic factor necessary for vitamin Center. Uttirmity of ll'ircnitsfn. tithmucosa arc distinctly dysphttlic pat 11,, absorption. Invasion of the muscu- Afadfiort 5J706 terns, '| hr experimental concentration laris mucosae and tubmiieota by the of hiphcnyli (JUO ppm) within the diet epithelial elements may lead to loss of H< fcrrurtl ist Nutt which was sufficient to produce these conditions in subhuman primate* in 3 mo n i Its it alxwtt ten tinsci the level* that have occurred in tampict of milk (2K ppm) and of fhh (33 ppm) re potted by llte U.S. f?ood and Drug Admittitliaiton This concentration is much let* than the level* that have <Kcurled in food products due to In integrity of the gastric wail with even tual erosion, ulceration, and hemor rhage. as was rite case in monkeys fed chlorinaird biphenyl dioxins (12), Because interest in these environ mental contaminants tj only recent, invexiigative efforts hate not yet deter mined the long-term carcinogenic poten tial of t'CB'a and J'C.'T's. The aisocta- i. n. w. p:,tvm-rx. r. sucuv. t>. it. ruiaii, S. G. tfcrmjin, M. N. Ktncp. Kitiurt Hi, im (IW-W. 2* A. C. /Tnfp(b, Mrol/l' I'clfrrt. ff If 0*72V J G. r4 Frit', thi^ p, SS. 4. A. R. YoVb. <HJ.t f. 19. . >. M Kuuuufld, T. YoO'hB'i, J. Unuj'li A. Y*'.w'ihKi, fbht, p tl9, 4. G. vci. ifijt p. tot. 1. |3. U. KfsrJ.drk ut t. K. Allrn, t*J. tf+t. fli (IJT0>, I, M. Ki<9i/44fnJ, Jrrh. Cn%irp*i. t'mUk 11, r dustrial accidents (2000 to 3000 ppm) lion of ehronie irritation with catteer. f. J. I.. I.ncgr U. tJ> P`fkt*U, <31. patticularly of the stomach, cervix, oral n> {jtift. The magnitude of the chronic ef fects which could he ptoJuccd by I'CU- nutcosa. and bronchial epithelium, is well documented. These dyspl-xxtic cel to. Vt. Ofn* >wtwrt.a-Ifdtijj /rtWi/, <]. 74 <19711. IL /. WIMAII Mi II, c. Cecil, t. Attic. i ttt'Juecd hypcniorltic f.ntntis it as yet lular abnormalities of the hypertrophic f hrm I*. IH'I rf70l- |). }, It. Alim L A Cj-'itui. A**", t. imdricrmiited. The ttausca and vomiting gastric mucosa arc hl.cly due to chronic IVt. Rfi. 71, jn <19611- following human consumption of J'CtTs irritation bus are at present short of tJ, TKik J| MipreMlJ b| K|j| (MVl &HM11 a.kR K00l*jt 3 tO SS'JuMiiifl 5> a ate possibly a result of the gastric irrita neoplastic transformation. The develop CfM fJVftML tr . tions. Weight loss by she experimental ment of hypertrophy, hyperplasia, and Ml ^tailwi Mil 2 / J4lLfAKY t72 *9 i HONS 20454S m*'