Tags

Type your tag names separated by a space and hit enter

Iron-free neoplastic nodules and hepatocellular carcinoma without cirrhosis in Wistar rats fed a diet high in iron.
J Pathol. 2006 Jan; 208(1):82-90.JP

Abstract

Although excess hepatic iron in hereditary haemochromatosis and dietary iron overload in the African causes hepatocellular carcinoma, it usually does so in the presence of cirrhosis. A direct hepatocarcinogenic effect of iron has not been proved. Moreover, an animal model of hepatocellular carcinoma induced by iron overload has not been available. The aim of this study was to develop such a model and to use it to ascertain whether excess hepatic iron is directly hepatocarcinogenic. Sixty Wistar albino rats were fed a chow diet and 60 the same diet supplemented initially with 2% carbonyl iron for 12 months, followed by 0.5% ferrocene for 20 months. Five rats from each group were sacrificed every 4 months for 24 months for histological and biochemical monitoring. By 16 months, hepatocytes in all the rats receiving the iron-supplemented diet showed grade 4 iron overload, comparable in degree with that seen in patients with advanced hereditary haemochromatosis and dietary iron overload. Altered hepatic foci and pre-neoplastic nodules were first seen at 16 months. These increased in size and number with time, were iron-free, stained positively with placental glutathione sulphydryl transferase, and showed the same histological features as the iron-free foci described in patients with hepatocellular carcinoma complicating hereditary haemochromatosis. At 32 months the eight surviving rats in the iron overloaded group were sacrificed. The livers of five of these rats contained pre-neoplastic nodules and one showed, in addition, an iron-free, well-differentiated hepatocellular carcinoma. The tumour stained positively for placental glutathione sulphydryl transferase. Neither cirrhosis nor portal fibrosis was present in this or any iron-loaded animal. We conclude that hepatocellular carcinoma may complicate dietary hepatic iron overload in Wistar albino rats in the absence of fibrosis or cirrhosis, confirming an aetiological association between dietary iron overload and the tumour and suggesting that iron may be directly hepatocarcinogenic.

Authors+Show Affiliations

MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand and Johannesburg Academic and Baragwanath Hospitals, South Africa.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16278820

Citation

Asare, George A., et al. "Iron-free Neoplastic Nodules and Hepatocellular Carcinoma Without Cirrhosis in Wistar Rats Fed a Diet High in Iron." The Journal of Pathology, vol. 208, no. 1, 2006, pp. 82-90.
Asare GA, Paterson AC, Kew MC, et al. Iron-free neoplastic nodules and hepatocellular carcinoma without cirrhosis in Wistar rats fed a diet high in iron. J Pathol. 2006;208(1):82-90.
Asare, G. A., Paterson, A. C., Kew, M. C., Khan, S., & Mossanda, K. S. (2006). Iron-free neoplastic nodules and hepatocellular carcinoma without cirrhosis in Wistar rats fed a diet high in iron. The Journal of Pathology, 208(1), 82-90.
Asare GA, et al. Iron-free Neoplastic Nodules and Hepatocellular Carcinoma Without Cirrhosis in Wistar Rats Fed a Diet High in Iron. J Pathol. 2006;208(1):82-90. PubMed PMID: 16278820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iron-free neoplastic nodules and hepatocellular carcinoma without cirrhosis in Wistar rats fed a diet high in iron. AU - Asare,George A, AU - Paterson,Alan C, AU - Kew,Michael C, AU - Khan,Shehnaz, AU - Mossanda,Kensese S, PY - 2005/11/10/pubmed PY - 2006/1/31/medline PY - 2005/11/10/entrez SP - 82 EP - 90 JF - The Journal of pathology JO - J Pathol VL - 208 IS - 1 N2 - Although excess hepatic iron in hereditary haemochromatosis and dietary iron overload in the African causes hepatocellular carcinoma, it usually does so in the presence of cirrhosis. A direct hepatocarcinogenic effect of iron has not been proved. Moreover, an animal model of hepatocellular carcinoma induced by iron overload has not been available. The aim of this study was to develop such a model and to use it to ascertain whether excess hepatic iron is directly hepatocarcinogenic. Sixty Wistar albino rats were fed a chow diet and 60 the same diet supplemented initially with 2% carbonyl iron for 12 months, followed by 0.5% ferrocene for 20 months. Five rats from each group were sacrificed every 4 months for 24 months for histological and biochemical monitoring. By 16 months, hepatocytes in all the rats receiving the iron-supplemented diet showed grade 4 iron overload, comparable in degree with that seen in patients with advanced hereditary haemochromatosis and dietary iron overload. Altered hepatic foci and pre-neoplastic nodules were first seen at 16 months. These increased in size and number with time, were iron-free, stained positively with placental glutathione sulphydryl transferase, and showed the same histological features as the iron-free foci described in patients with hepatocellular carcinoma complicating hereditary haemochromatosis. At 32 months the eight surviving rats in the iron overloaded group were sacrificed. The livers of five of these rats contained pre-neoplastic nodules and one showed, in addition, an iron-free, well-differentiated hepatocellular carcinoma. The tumour stained positively for placental glutathione sulphydryl transferase. Neither cirrhosis nor portal fibrosis was present in this or any iron-loaded animal. We conclude that hepatocellular carcinoma may complicate dietary hepatic iron overload in Wistar albino rats in the absence of fibrosis or cirrhosis, confirming an aetiological association between dietary iron overload and the tumour and suggesting that iron may be directly hepatocarcinogenic. SN - 0022-3417 UR - https://www.unboundmedicine.com/medline/citation/16278820/Iron_free_neoplastic_nodules_and_hepatocellular_carcinoma_without_cirrhosis_in_Wistar_rats_fed_a_diet_high_in_iron_ L2 - https://doi.org/10.1002/path.1875 DB - PRIME DP - Unbound Medicine ER -