Rat Liver Parenchymal Cell Function during Azo Dye Carcinogenesis.

(I†• tagged) rose bengal uptake-excre tion test for liver function, as described by Taplin et al. (21), has proven to be a valuable test for a quantitative measure of liver function. In rats, I†• rose bengal uptake and excretion are definitively related to parenchymal cell function (21). Mendeloff (10) showed by fluorescence that injected rose bengal is localized only in parenchymal cells of the liver and cannot be found in the Kupffer cells. Meurman (11) presented autoradiographic cvi dence that rose bengal intralobular distribution is mainly centrilobular. The dye is not metabolized by the liver and very little is found in the extravascular spaces (3, 4). In the study of impaired liver function in rats fed the hepatocarcinogen N-2-fluorenyldiacetamide, Morris el al. (15) showed that a progressive decrease iii excretion of rose bengal occurred from the second to the tenth week of carcinogen feeding. Important changes have been observed in the liver parenchyma during azo dye hepatocarcinogenesis: the parenchymal cell population is reduced (7) ; there is de creased basophilia (16) as well as degenerative changes followed by necrosis (18). These morphologic changes were found to originate in the region of the central vein; they coalesced with similar changes in adjacent lobules and preceded abnormal regeneration and tumor formation occurring in periportal regions. The early effects of feeding a carcinogen, DAB, and a noncarcinogen, 2-Me DAB, on liver parenchyma function, as studied by means of rose bengal chromoexcretion, are reported in this paper. MATERIALS AND METHODS Male Wistar rats (200 grn) were fed a basal diet low in protem (12, diet 3), containing 0.06 % DAB or 2-Me DAB. A control group received the basal diet alone. After the experimental diets were fed, laparotomy was performed at various intervals under Nembutal aiies thesia in rats of all three groups. The common bile duct was exposed, ligated at about 10 mm from the duodenum, and cannulated by inserting a 26-gauge needle (to which was fitted a polyethylene tube, I.D. 0.018 in.) approxi mately 5 mm above the ligature. One milliliter of a solution of radioactive rose bengal in saline, containing 1 mg of the dye with a radioactivity of 5 mc, was injected in the right femoral vein. Blood samples (10 Mi) were collected from the tail vein over a period of 3 hr. Samples of bile (5 M) were collected from the cannula during the same period. The …