Abstract |
The present study was designed to determine the long-term effects of orotic acid (OA), a multi-organ tumor promoter, in rats not exposed to any carcinogen. Male Fischer 344 rats (130-150 g) were divided into two groups and given either a semisynthetic basal diet (BD) or the same diet containing 1% OA. Animals from both groups were killed after 1 or 2 years of treatment. Foci of placental glutathione-S-transferase (GST 7-7) positive hepatocytes were observed in the livers of both BD and OA fed rats killed after 1 year. However, they were more in number in animals receiving OA (156 +/- 21 versus 51 +/- 11/cm3). After 2 years, hepatic nodules were seen in almost all the animals given OA and in approximately 30% of the rats given BD. The nodules were of two main types: (i) a reddish-brown type, present in 85% of rats exposed to OA and in 27% of rats given BD, and (ii) a greyish-white type, found in 50% of animals fed OA and in none of the animals fed BD. These two types of lesions were also histologically different. Reddish-brown nodules were composed of slightly enlarged hepatocytes resembling normal surrounding tissue, while greyish-white nodules were similar in structure and are indistinguishable from hepatic nodules induced by genotoxic chemical carcinogens. The results are interpreted to suggest that the foci/nodules seen in OA-fed rats are due to a promoting effect of OA on spontaneously arising and/or diet-induced altered cells.
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Authors | E Laconi, S Vasudevan, P M Rao, S Rajalakshmi, P Pani, D S Sarma |
Journal | Carcinogenesis
(Carcinogenesis)
Vol. 14
Issue 9
Pg. 1901-5
(Sep 1993)
ISSN: 0143-3334 [Print] England |
PMID | 8104733
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Orotic Acid
- gamma-Glutamyltransferase
- Glutathione Transferase
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Topics |
- Animals
- Fat Necrosis
(chemically induced, pathology)
- Glutathione Transferase
(metabolism)
- Incidence
- Liver
(drug effects, enzymology, pathology)
- Male
- Organ Size
(drug effects)
- Orotic Acid
(administration & dosage, pharmacology)
- Rats
- Rats, Inbred F344
- Time Factors
- gamma-Glutamyltransferase
(metabolism)
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