Peroxisomal enzyme induction uncoupled from enhanced DNA synthesis in putative preneoplastic liver foci of rats treated with a single dose of the peroxisome proliferator nafenopin.
Putative preneoplastic foci of spontaneous origin could be detected in the livers of 2 year old, untreated male Wistar rats. The unaltered and preneoplastic hepatocytes showed an identical expression of the peroxisomal marker enzyme acyl-CoA oxidase, as determined by immunohistochemical staining. A single dose of the peroxisome proliferator (PP) nafenopin (NAF) induced the enzyme predominantly in hepatocytes around the central venules and cell replication mainly in the periportal areas. However, upon one NAF application almost all of the preneoplastic foci showed a considerably weaker immunoreaction for peroxisomal acyl-CoA oxidase than the surrounding tissue. Concomitantly NAF elevated replicative DNA synthesis index in foci up to approximately 40%, while replication of hepatocytes in the unaltered portion of the livers increased only slightly to moderately. In conclusion, NAF-induced peroxisomal acyl-CoA oxidase and replicative DNA synthesis seem not to be necessarily coupled within the same liver cell. Furthermore, preneoplastic foci responded rather to the cell replicative than to the peroxisomal effects of NAF, suggesting that the PP-induced growth stimulus is of particular significance for the carcinogenic action of this class of compounds.
Grasl-Kraupp
B
B
Institut für Tumorbiologie-Krebsforschung, Universität Wien, Austria.
Huber
W
W
Timmermann-Trosiener
I
I
Schulte-Hermann
R
R
D042962:Acyl-CoA Oxidase; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology* / Q000648:ultrastructure; D009255:Nafenopin / Q000633:toxicity*; D010088:Oxidoreductases / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013936:Thymidine / Q000378:metabolism
D002273:Carcinogens; D004273:DNA, Neoplasm; D009255:Nafenopin; D004247:DNA; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; D013936:Thymidine