ASSESSMENT OF THE INFLUENCE OF SUBACUTE PHENOBARBITONE ADMINISTRATIONON MULTI-TISSUE CELL-PROLIFERATION IN THE RAT USING BROMODEOXYURIDINEIMMUNOCYTOCHEMISTRY

The effects of daily administration of phenobarbitone on the mitotic r ates of several tissues were investigated by bromodeoxyuridine (BrdU) immunocytochemistry. Phenobarbitone (80 mg/kg per day) was dosed to AP Wistar male rats for up to 7 days and BrdU (10 mg/ml) was given by in fusion at a rate of 10 mul/h via subcutaneously implanted osmotic mini pumps for 2 days prior to necropsy on days 1, 2, 3, 5 and 7. BrdU-labe lled nuclei were visualised by peroxidase-antiperoxidase immunocytoche mistry and counts of the numbers of labelled cells (labelling index, L I%) made from at least 1000 cells per tissue section(s). The LIs of se veral tissues (testis, adrenal cortex and medulla, kidney distal convo luted tubule and exocrine pancreas) showed no statistical difference b y comparison with controls. Several tissues exhibited characteristic r esponses to phenobarbitone administration. Pituitary and endocrine pan creas LIs were decreased while those of thyroid, liver and kidney prox imal convoluted tubule were increased. The pattern of LI increase was unique to each tissue with liver (median and lateral lobes) increased two-fold on day 3 and returning to control levels thereafter while kid ney proximal tubule LI rose gradually with time and remained elevated on day 7. Thyroid LI on day 1 was almost double that of day 0 control and increased steadily thereafter. These data illustrate the varied re sponses of different tissues to phenobarbitone exposure, namely, depre ssion and stimulation of mitosis. The causation of these functional ch anges is discussed in relation to direct and indirect effects on funct ional parameters, especially enzyme induction, alterations in hormonal and growth factor status and receptor regulation.