293

THOROTRAST LIVER TUMOURS

A.Sarago~a~ M.P.Rocha~ M.D.Patuleia~ M.B.RodriBues and J.da Silva Horta Center of Gastroenterology, University of Lisbon (INIC) and Pathological Institute - Faculty Medicine of Lisbon

In the sequence of previous works, the AA performed a study in 13.962 necropsies from 1957 till December 1984. In this group, the AA found 168 primary malignant liver tumours, and 33 were injected with thorotrast (ThO2). From the 168 tumours 126 were hepatocellular- carcinomas, 22 cholangiocareinomas and 20 angiosarcomas. From the 33 thorotrast liver tu- mours, 2 were hepatocellularcareinomas, 12 cholangiocarcinomas and 19 angiosarcomas. In 19 thorotrast liver tumours the AA could study the clinical evolution: all patients refered only dispeptic disturbances during 25 to 40 years after the injection, as soon as they start having weight loss, weakness, anorexia, with pain in the right upper quadrant abdomen, jaun dice and ascites, death occurred no longer than 9 months. In all of these patients the bio chemical data (protein electrophoreses, aspartate serum transaminases, alkaline phosphatase-- and ~glutamyltranspeptidase, showed high values and the alphaphetoprotein was always nega- tive including the hepatoeellularcarcinoma. In conclusion: angiosarcoma was the primary malignant liver tumour more frequent in patients injected with thorotrast, cholangiocarcino ma was, in frequence, the second tumour and the hepatoeellularcarcinoma the less frequent. The clinical evolution, the biochemical data and the alphaphetoprotein determination were similar in all patients with thorotrast liver tumours.

COLLAGEN GENE EXPRESSION IN HEPATIC FIBROSIS: mRNA LEVELS OF TYPE I, I I I AND IV COLLAGENS IN HEPATIC FIBROSIS INDUCED BY DIMETHYLNITROSAMINE (DMN) IN THE RAT

294 E-R. Savolainen, L. H~m~l~inen, T. Pihlajaniemi, J.C. Myers*,K.I. Kivirikko Collagen Research Unit, University of Oulu, Oulu, Finland and * Connective Tissue Research Inst i tute, University of Pennsylvania, Philadelphia, U.S.A.

Liver f ibrosis was induced in 42 adult female rats by i .p. injections of DMN (I ml of a I% solution in saline per kg body wt.) given on the f i r s t 3 days of each week for a 3-week period. Some of the non-treated control animals were ki l led in the beginning of the experi- ment and some on days 7, 14 and 21 together with the treated rats. The l ivers were analyzed for hydroxyproline and two of the enzymes catalyzing post-translational modifications of collagen, prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase. Total l iver RNA was extracted and assayed by dot blot hybridization using the following cDNA probes:~12 for pro~1(1)[1], Hf32 for pro~2(1)[2], E6 for pro~1( l l l ) [1] and HT21 for proa1(IV)[3]. After 7 days there was a signif icant increase in the collagen synthesis enzymes but no change in the collagen content of the l iver. At the same time the mRNAs of type I, I l l and IV colla- gens were increased being all about 1.5 times those in the controls. On day 14 a sl ight in- crease was observed in hepatic collagen content, which by day 21 showed a signif icant 4-fold increase. Significant increases of 2 to 6-fold were observed in al l collagen mRNAs on day 14, the most prominent elevation being found in that of type IV collagen. The mean increase in collagen mRNA was about 400% by the end of the experiment. I t thus seems that during fibrogenesis hepatic collagen mRNA content and collagen synthesis enzymes are increased be- fore any collagen accumulation can be detected. Later, collagen accumulation occurs in par- allel to the rise in mRNA levels. Procollagen mRNA measurements may thus provide early information on collagen synthesis rates and expression of different collagen types in experimental f ibrosis and perhaps also in patients with l iver diseases. Refs.: [ I ] Loidl et al, Nuclei Acids Res 1984;12:9383; [2] Myers et al, Proc Natl Acad Sci USA 1981;78:3516; [3] Pihlajaniemi et al, J Biol Chem, in press.

$325