Abstract

The effects of dietary iron deficiency on induction of putative preneoplastic, gamma-glutamyltransferase (GGT)-positive hepatocyte focal lesions in the liver of rats treated with diethylnitrosamine (DEN) followed by phenobarbital (PB) were investigated. Male Fischer 344 rats of 4 weeks old were placed on an iron deficient (ID) diet containing less than 5 p.p.m. of iron or an iron supplemented (IS) diet containing 180 p.p.m. of iron throughout experimental period of 12 weeks. Both groups of rats were administered 200 mg kg-1 body weight of DEN by a single intraperitoneal injection at Week 4 followed by PB mixed into each diet at a concentration of 0.05% from Week 6 to the final sacrifice at Week 12 when induction of GGT-positive foci was quantitatively analysed. On the ID and IS diets, respective numbers of GGT-positive foci were 6.3 and 14.2 cm-2. The sizes of foci were not altered by the iron content of the diet. The present results indicate that iron plays a role in the development of preneoplastic foci in the livers of rats initiated with DEN and promoted by PB especially in the initiation phase.

Highlights

  • We examined the effects of dietary iron deficiency on induction of GGT-positive hepatocyte foci in rat liver initiated with diethylnitrosamine (DEN) and promoted by phenobarbital (PB) in order to cast further light on a role of iron in rat chemical carcinogenesis

  • Inhibitory effect of dietary iron deficiency on induction of GGT-positive foci in the liver of rats receiving DEN initiation followed by PB promotion (Experiment 1)

  • In all of the groups, GGT-positive foci were developed. Those foci were histologically characterised as acidophilic foci with ground glass appearance constituted by more than 10 altered hepatocytes with hyperchromatic and enlarged nuclei containing prominent centrally located nucleoli according to the criteria described by Institute of Laboratory Animal Resources, National Research Council, National Academy of Sciences, Washington, DC (1980)

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Summary

Methods

Male Fischer 344 rats were obtained at 3 weeks of age from. Japan SLC, Inc., Hamamatsu, Shizuoka, Japan and used after being acclimatised for 1 week with free access to Oriental MF Diet (Oriental Yeast Co. Ltd., Itabashi, Tokyo, Japan). The animals were housed in iron-free plastic cages in an air-conditioned room maintained at 25°C with a 12 h dark/light cycle and allowed access to food and tap water ad Correspondence: D. Received 20 February 1991, and in revised form 10 June 1991. The experiments were started by placing rats on the prepared diets after fasting fcr 18 h on the last day of their acclimation

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