Biology of the Cell, Volume 63, 1988

TISSUE INJURY AND REPAIR IN THE RAT KIDNEY AFTER EXPOSURE TO THE ANTICANCER AGENTS CISPLATIN AND CARBOPLATIN. D. NONCLERCQ I, V. YERNAUX I, G. TOUBEAU I, G, LAURENT 1'2 and J.A. HEUSON-STIENNONI.lservice d'Histologie et de Cytoleqle exp~rimentale, Facult@ de M~declne, Unlverslt~ de l'Etat ~ Mons, Avenue du Champ de Mars, 24, 7000 MONS (BELGIUM) 2Unlversit~ Cathollque de Louvaln and I.C.P., BRUSSELS (BELGIUM).

Cisplatln (cis~dlamminedlchloroplatlnum ll), a potent antitumour drug, is used in clinics to treat a variety of neoplasms. Treatment with this agent can however lead to renal dysfunction, which is considered as the major dose-limltlng adverse effect. The present study is devoted to the renal tissue injury and repair after clsplatin administration to experimental anlmals. In this respect, cisplatln was compared with a more recently developed platinum salt, carboplatin (ci___ss-diam- mine-l,l-cyclobutane dlcarboxylate platinum If).

Female Sprague-Dawley rats were treated i.p. with either 8 mg/kg clsplatin (delivered in four consecutive daily injections) or ~0 mg/kg carboplatln (in one injection), and sacrificed ~, 7, I~ and 21 days after treatment. The kidneys were examined by llght and electron microscopy in order to evaluate : (1) the extent of drug-induced tissue injury, (li) the renal cell proliferation associated with renal tissue repair and perltubular infiltration (measured by the rate of [3HI thymldlne incorporation into DNA, (Ill) the cytological characteristics of cells involved in the proliferative response.

Although both cisplatln and carboplatln induced slmilar leslons and morphological abnormalities in renal tissue (tubular necrosis, hydroplc degeneratlon and long-lasting cystic dilatlon), the tissue alterations were much less prominent after carboplatln administration. Accordingly, the degree of cell proliferation and morphologlcal evidence of tubular regeneration were also reduced in carboplatln-treated animals.

Altogether, these data point to a lesser nephrotoxlcity of carboplatin, as compared to clsplatin.

ETUDE DES REPONSES OSTEOGENIQUES INDUITES PAR DES IMPLANTS COMPOSITES TITANE-BIOVERRE.

Ko LETE, M.P. FRANCK-DUFIEF, R. SHERIDAN, J.A. HEUSON-STIENNON. Service d'Histologle et de Cytoloqle exp~rimentale, Facult~ de M~declne, Universlt~ de l'Etat ~ Hens, Avenue du Champ de Mars, 24, 7000 MONS (BELGIQUE).

Nous averts ~tudi~ le comportement "in vlvo" dans des tibias de rats, d'implants composites cons- tltu~s d'une plaque;re de tltane sur laquelle le bloverre AI P1 SI0 (Brevet) a ~t~ projet~ A l'alde d'une torche ~ plasma. Ce bloverre AI PI SI0 sons forme d'implant massif, a ~t~ s~lectionn~ pour sa blocompatibillt~ et sa parfalte Int~gratlon dans les tissus hSteso (Re SHERIDAN et ale, Silicates Industrlels, 1987/9-10, 135-140). LWutilisation des implants composites "tltane-bloverre" nous permet, cette folsj de comparer, au seln d'un m~me animal et d'un m~me tibia, la bior~actlvlt~ du bloverre proJet~ ~ celle du t i t a n e qui e s t courauunent u t i l i s ~ comme mat~r iau p r o t h ~ t i q u e .

Des ~ tudes , par m i c r o s c o p i e o p t i q u e , avec e t sans d ~ c a l c i f i c a t i o n , nous ou t permis de q u a n t i f i e r e t d ' ~ v a l u e r le degr~ de m i n ~ r a l i s a t i o n des d i v e r s t i s s u s d~velopp~s au c o n t a c t de l~ imp lan t . L ~ u l t r a s t r u c t u r e des t i s s u s n~oform~s aux abords du b i o v e r r e a ~galement pu 8 t r e p r~c i s~e su r l e s ~ c h a n t i l l o u s non d ~ c a l c i f i ~ s .

D~apr~s nos o b s e r v a t i o n s morphologiques , q u e l l e que s o i t l a dur~e d ~ i m p l a n t a t i o n (1 ~ 15 m o i s ) , l e s r~ponses os t~og~niques au c o n t a c t du b i o v e r r e s en t s u p ~ r i e u r e s ~ c e l l e s r e u c o n t r ~ e s au n iveau du t i t a n e o~ du t i s s u f i b r e u x r e s t s t ouJour s p lu s ~ tendu. Cependaut, par l a m i c r o s c o p i e o p t i q u e sans d ~ c a l c i f i c a t i o n , nous avons re~arqu~ que la l i a i s o n du t i s s u osseux au b i o v e r r e se r ~ a l i s e par l ~ i n - t e rm~d ia i r e d~un t i s s u o s t ~ o i d e non min~ra l i s~ (Yon Kossa n ~ g a t i f ) . Nos ~ tudes u l t r a s t r u c t u r a l e s cor- r obo ren t ces r ~ s u l t a t s . En e f f e t , pour la maJor i t~ de l ~ i n t e r f a c e " o s - b i o v e r r e " , nous remarquons l a p resence d~une mat r ice c o l l a g ~ n i q u e dense , peu c e l l u l a r i s ~ e , dans l a q u e l l e a p p a r a i s s e n t p a r f o i s des amas c r i s t a l l i n s , Au n iveau de c e r t a i n e s zones v a s c u l a r i s ~ e s , nous o b s e r v o n s t o u t e f o i s une p o p u l a - t i o n c e l l u l a i r e p lus i m p o r t a n t e . Les f i s s u r e s du b i o v e r r e sen t c o l o n i s ~ e s par du m a t e r i e l o rgan ique e~ des prolongements c e l l u l a i r e s .

En conc lus ion , l e b i o v e r r e A1 P1 S10 permet un s c e l l e m e n t r ap ide e t d u r a b l e sous sa forme p r o - J e t ~ e par l ~ i n t e r m ~ d i a i r e d ' un t i s s u o s t ~ o i d e .

ALTERATIONS OF PEROXISOMES IN MOUSE VIRAL HEPATITIS. M. LANGENDRIES ([), A. BINGEN (2) and F .REELS (I) (I) Human An~o~, V~e Gr~_v~4~ ~u44~, ~(14~e~ac~t 103, I0~0 ~u4~e~, GrLd (22 Labo~aZoJ.ae de VJ~olo~Le de la Facui~ de ~4deci~e, gnivea~t~ Loui~ ?a~, 5~a~bou~.

Data on peroxisomes in hepatitis are fragmentary because related to individual patients and to different stages and types of hepatitis. Balb/c mice were injected with MHV3 and fixed by perfusion 24, 40 and 48 h after inoculation. Control animals were injected with PBS and perfused 48 h later. Staining for catalase was performed with diaminobenzidine. By light microscopy, the number of peroxisomes decreased as the delay between infection and fixation was longer;this was already visible after 24 h. Were peroxisomes indeed destroyed or did they simply escape light microscopical observation? Peroxisomes were counted in electron micrographs;the hepatocyte area was measured by the IBAS system. When fat droplets were taken into account, the number of peroxisomes per unit area was significantly lower in the 48 h specimen than in the control animal;when fat was excluded, numbers were not significantly different,which proved that the large amount of fat in the 48 h liver was responsible for the apparent decrease. Area of the perexisomes measured by the IBAS system was significantly lower after 48 h than in the control (p <O,0001);this led to a lowered volume density in the 48 h specimen when compared with the control. Staining of the individual peroxisomes was clearly diminished in the 48 h specimen. Rare images suggesting diffusion of enzyme into the surrounding cytoplasm were observed after 24 h and became frequent after 40 h: a halo was visible between the peroxisomal matrix and the membrane. Changes in the peroxisomal staining were present as early as after 24 h while no other kind of cell pathology could be seen: the other organelles were morphologically normal.Morphological alterations appeared for the first time after 48 h: fat vacuoles were abundant and several areas developed inside which only few pycnotic nuclei and fibrin were visible; all the other organelles were completely destroyed. In conclusion, this examination of hepatitis revealed an early decrease of catalase staining and a decrease of peroxisomal size, causing a decrease in volume density. Supp. by FGWO 3.0071.83, 3.0034.86.

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