The repeated administration of the hypolipidemic agent Su-13 437 (nafenopin) to neonatal rats roughly doubled the number of peroxisomes in the liver tissue and caused a sixfold volumetric expansion of the peroxisomal compartment. During the proliferative response, the size-distribution of the peroxisomes was reversibly altered, enlarged particles appearing in numbers varying according to the dose given. By means of a new method for quantitative autoradiography, it was shown that (a) the concentration of silver grains over peroxisomes was comparable to that found over the endoplasmic reticulum; (b) the peak incorporation of [aH]arginine into the peroxisomes was delayed in comparison with that into the endoplasmic reticulum; (c) the label, once incorporated into the expanding peroxisomal compartment, displayed the same shift to large particles as did the whole population. These results are compatible with the biosynthetic pathway for peroxisomal catalase proposed earlier (cf. reference 12), and with the notion that the druginduced size-shift might have resulted from progressive growth of a particular class of peroxisomes formed in the presence of the agent. Evidence is presented to show that during the recovery period the larger peroxisomes are removed preferentially.In a series of reports, we have shown that two hypolipidemic drugs of the a-aryloxyisobutyric acid type, clofibrate (CPIB) 1 and CIBA Su-13 437, are endowed with the capacity to elicit the induced state and to expand the peroxisomal compartment of male rat liver parenchymal cells (24-1Abbreviations used in this paper: CPIB, clofibrate, Atromid S; DAB, diaminobenzidine; ER, endoplasmic reticulum; PO, peroxisome(s) (microbody); RER, rough-surfaced endoplasmic reticulum, SER, smoothsurfaced endoplasmic reticulum; Su-13 437, CIBA Su-13 437 (nafenopin). 26, 69). These observations were subsequently confirmed and extended by several research groups (reviewed in references 2, 30, 56, 70). The biosynthesis and precise metabolic function(s) of peroxisomes (microbodies) in normal or in experimentally altered mammalian cells are still not fully understood (12,13,56,70), although in the past few years considerable progress has been achieved with regard to the biosynthesis of peroxisomal constituents (37,38,62). In addition, interest in the biology of peroxisomes has been rekindled by a large number of morphological observations leading to the concept of the ubiquitous distribu-

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The changes induced in the liver epithelium of male rats by two dibenzobicyclo octadiene analogues, maprotiline and benzoetamine, were compared. Maprotiline at high dose levels produced induction of microsomal membranes and of constituent enzymes of the endoplasmie reticulum (ER), preceded by the appearance of altered peribiliary structures, part of which showed the morphological aspect of myeloid bodies. These particles, which appeared to develop at the expense of peribiliary dense bodies, were considered to be of a lysosomal nature by virtue of their acid phosphatase activity. All the hepatic changes induced by maprotiline proved to be reversible upon cessation of treatment. Since changes similar to those caused by maprotiline were also induced by amitriptyline, imipramine and chlorpromazine, they may conceivably be produced nonspecifically by lipophilic bases. Benzoctamine, being of a less basic nature, was found to induce reversible hypertrophy of the SER only.