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Long-term studies on chemically induced liver enlargement in the rat III. Structure and behaviour of the hepatic nodular lesions induced by ponceau MX

1977; Elsevier BV; Volume: 7; Issue: 3 Linguagem: Inglês

10.1016/0300-483x(77)90051-8

1879-3185

P. Grasso, Tim J.B. Gray,

Carcinogens and Genotoxicity Assessment

When Ponceau MX was given at 2.5% levels in the diet to female Wistar rats for 5–30 weeks the liver became enlarged but histologically it appeared normal. Subsequently, pathological changes appeared consisting first of cell enlargement, then of abnormal glycogen deposits and later still by irregular areas of fatty change and nodular hyperplasia. The progress of these lesions was followed by feeding Ponceau MX to female rats for 12 months then performing a laparotomy and returning them to a normal diet for a further period of 9 months. Approximately half the animals had no nodules at laparotomy and these were free of nodules at autopsy. The remainder had nodules ranging in size from 2–10 mm diameter at laparotomy and all of these had grown to varying extents so that at autopsy, the diameter of the nodules ranged from 3–30 mm. Histologically, the smaller lesions consisted of single nodules made of regular cords of cells, the larger lesions comprised a conglomeration of nodules, some of which were solid and other exhibited advanced fatty change. In turn the solid nodules were made up of normal or enlarged cells that were either disposed in regular cords or formed papillary and adenoid structures. Such structures were associated with pulmonary metastases. Fibrous bands were occasionally present between nodules. Administration of [3H]thymidine revealed that uptake was most pronounced in the solid nodules both when the animals were maintained on Ponceau MX for 21 months and when treated for only the first 12 months. These investigations indicate that histological changes precede the appearance of hepatic nodules in Ponceau MX-treated rats suggesting that initially they are of a reactive nature. Once established the nodules continue to grow and may either develop fatty degeneration or become malignant.