Document ZbNz08Z2DJegx3zMY0djrJDO

12/31/97 10:19 ._ I I DW(E UNIU. E D CTR LIBRFlRY @&31 ~ Q Springer-Verlag 1996 .eccived: 20 Julie 199.5 Acccpted: 21 A U P U O1~995 I I 1 rhtnct Subslanlially more cases of tvbular d&ape developmentof renal cell cancer after exposureto trich- ,ere found timong renal a l l carcinoma patient! who loroethylene {Goepttlt et al. 1995). ad been exposed io high levels of trichloruethylene I n the context of recognition of occupational dis- Iter inany years than among renal cell carcihoma eases, 17 patients who bad been e x p s d to high levels latients who had not been exposed to trichlorhrhy- of trichloroe~hybreover many years and who later :ne. This supports ihe hypothesis (Goeptar et al.11995) were diagnosed wifh renal cell cancer, have been as- :hat chroiiic tubular damage may be regarded as;a ne- sessed at our institute. w r y precondition for tricbloroethylene lo exert In all these patienls, prenarcotic symptoms such as nephrocarcinogmic effect. The findings also in&icate a feeling ofdrunkenness,dizziness,headacheand dtow- hat the urine prolein patterns identified wid1 /SDS- siness had occurred frequently inconnection with thcir 'AGE may represent a valuable parameter for ;effect psst occupational exposure to trichloroclhylene. The iomonitoring of persons exposed to tii& lev+ls of workers often left the work awd for short intervals to dchloroethyleneover many years. I "wcupemte" in fresh air. Tjpical occupational activ- -I w& Trichloroethylene Renal cell cancer ities wcre degreasing of metal wares, production of rubber boxes for storage of batteries, welding of metal 'ubular damage I surfaces wwred With trichloroethylene, clcanitrl; and decreasing activities in thc textile industry and cleaning ir, of felts and sieves in cardboard machines. In a number L recent epidemiological study. published in Arthires f Toxicology (Henscbler et al. 1995).has describkd an -sed incidence of renal cell cancer in inddstrial 'orktrs in Germany who had been exposed to: very %h ievels of trichloroethylene over many jears. p i n t of thc discussion was tha1 the observatiQnsin [posed humans were corroborated by mechapistic asiderations of I gluiathimedepmdmt toxifiaation uhway leading lo reactive nephrotoxic and nebhro- ucfnogtnicintermediatesof tricbbrwhylene. i lhispublication has promoted discussion on hbman *W n q p k . i l y ortrichloroetbykne.A rGcent extdnsin of the published data regarding toxicild and -enicity of t r i c h l o r m h y h has partic\rlady brward the argument that in any case, chtonic md damage should always be a prerequisite f4r the I, *1 - - \Fining (e41 K. G o b . V. Hakropouloc. H.M.Bdc *tu lSir Arbcitsphpologic an der Universitdi Dorlmund %r. 67. M I 2 9 Donmund. Germany I of camthe workerswere exposed to hot wicbloroetby- lene vapours. The workers were cxpossd lo tricli- loroerhylenc under unacceptable hygienic working conditions.In general, hoods, ventilating systems and proledive gloves were not available. Mean data of exposure of this poup were: slarl of exposure 19S9, duration of exposure 15.2 years. Tbe mean time point of r e d cell carcinoma diagnosis was 1990* RE mean latency period was 30.4 years. The individual exposure data are available on request. In order to investigate the frequency of pathologic protein excretion patterns in renal ctll cancer palients not exposedto trichloroethyteneor similarsolvents, we examined 35 renal cell cancer patients from a !a= urological clinic. These hospital p a t h 1 6 wrm selected fromthe hospital register of tumor patients. T h e postopcrativc period after aephlectomy due lo renal a l l cmcm was comparable to that of chc 17 trichloroethylene exposed patients. A newly developed procedure was employed to differentiatethe urinary protein patterns ofihe patients of both groups. This was SDS-polyacrylamide gradient I 10: 20 DUKE UNIV. MED CTR LIBRRRY 002 I ekctmpbresis (SDSI+AGE) using "Phesl System'' (Pharmacia, Fteiburg), bilver-staining and consecutive laser densitometry.In cbntrast to a quantifative detor- mination of spbcific snieserum proteinsand of tubu- lar enzymesexcretedin the urine,this semi-quantitative method oflws the advaniageofa high-resolutionsepar- ation between approxidately20 di&mt urinary pro- teins according lo thejr ~nolwcularsize (Kierdorf et al. 1993). It is thus psible/todiffereniiatebetween differ- ent pathologic4 proteinpaitemsin the excreted urine which indicate tublard glomerular M mixed renal damage. I Determination and as&ssmcnt orthe urinary protein patterns of both groups 61patients was always carried out by the same clinical nephrologist who had been involved in the developltrent of the mahod. Analysis was carried out blind, wicliout any knowledgeof names hospitalpatients wilh renal cell Cantxr than in renal Caucer patients who had becn occupationally expo; to very high concentrations of tricblorocthyk. , occupational exposure to potentially nepbrotoxic stanceswas ascribedas the cause ofthe tubular dam in the hospital patients,expcct in orre case.This path had been exposed to perchlorwbylene between 19 and 1972 as a dry cleaner. in general, the present dau, althoujgb limited. a fully consistent with tbc concept that the rcachrna bolite, S-(1,2-d~~orvinyl)-L.cy6t~i~nCd,uces iiephr toxicity and proteinuria (Davis et nl. 1995) and u-i the concept (Goeptar el al. 1995) that developme, of chronic tubular damage should be regarded as prerequisite for induction of renal cancer by tricl toroeihylene, or exposure status of Ihe;patients. The results arc presmkd in Table 1. Protein acretion patierns which indipte tubular damage in the remaining kidney were idtatifid in df 17 dthe exam- ined renal cell cancer patients who had been e x p o d io hi@ kvels of tdchloroetbylene over maoy y m s . Six cases of sewre tubular dqmage, six cases of mDderate tubular damage, two casts ofminor tubular damage and three cases of mixed /glomcrular/tubular damage were identified. I Thirty-five hogpita1 pafknts without trichloroethy- lene exposurewere alsoexi)mined (TableI). Eighteen of time palients showed normal proteinexcretionpnttems. Tubular damage was idtnjtified in 12 patients. mixed gbrnerular/tubular darn* was identified in four pa- tients, and one pdient sboyed glomerular damage. Overall, a substantiaUy \owcr prevalence oftubular damage was found among the nm-exposed &roupd f Davis J. BIaktman D,Jolly E, Prckwood W, Kolaja G. Petr T (1995) S - ~ l . 2 - R i ~ b l o & y l ) - ~ - ~ syrpt h~rdaoxich in the NL%Zerhand W&Crabbit:charaetctkation Orpwtdnuri, and examinalionofthe pocerrtin)roleof axidativcinjurj. TOXIW Path123 487-4537 Goeptar A. Conimadeur 3. Van Ommen 8, Van Bladatn I' Vanaculcn N 11995) Murbdipm and kincrrcs oftrichloroeth: km in relptidn to box*Gtyand cnmuogcnicily. Chcm Res Toxi 001 S: 3-21 Henrdrkr D, Yamvakrs S, Luamcrt S,. D e k a ~W, Kmw B. Thornas1.U h K (199S)lacresfcdiacidemzM r e n a l d twnorc h II cohort of cardboard workers e~posedto trichbrocthenc A& T0ricOl69; Z91-299 KhrrdortH. Melzcr H, Mann H.sitbcrt ii( W 3 ) Difkmntiation of proteinsinpdyauylemidc&s by a modlficllrionoisilver staining for tho Pplasl sptmand a lascr densitometer. Elactrophorais I4 810-%22 I i