Abstract
The numbers of argyrophilic nucleolar organizer regions (AgNOR) stained by the one-step silver colloid method were counted in background hepatocytes and within eosinophilic foci, amphophilic foci, and neoplastic nodules developing in rats given diet containing one of the peroxisome proliferators, clofibrate, di-(2-ethylhexyl)phthalate (DEHP), dehydroepian-drosterone (DHEA), and 4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio acetic acid (Wy-14, 643), for 32 weeks after a single i.p. injection of diethylnitrosamine. The frequency of AgNORs was highest in amphophilic foci, followed by neoplastic nodules, non-lesional areas, and eosinophilic foci in the rats receiving basal diet alone or treated with clofibrate, DEHP or DHEA. In the Wy-14, 643 case the amphophilic foci and neoplastic nodules were again highest but the value for eosinophilic foci was greater over that for the background parenchyma. Mean numbers of AgNORs in non-lesional hepatocytes were elevated in rats treated with DEHP and Wy-14, 643 to 1.81 and 1.82, respectively, significantly different (p<0.05) from the control value of 1.69. The present results suggest that AgNORs may be a useful marker for predicting the hepatocarcinogenic potential of peroxisome proliferators with amphophilic foci demonstrating a particularly high proliferative activity judging from the observed AgNOR scores.