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© 1990 Oxford University Press

research-article

Dose-dependent effects of short-term dietary administration of the food additive butylated hydroxyanisole on cell kinetic parameters in gastro-intestinal tract

Hans Verhagen 1, Carina Furnée, Bert Schutte 2, Fré T. Bosman 3, Geert H. Blijham 2, Peter Th. Henderson 4, Foppe ten Hoor and C.S. Kleinjans 5

Department of Human Biology, University of Limburg PO Box 616, 6200 MD, Maastricht, The Netherlands
2Department of Internal Medicine, University of Limburg PO Box 616, 6200 MD, Maastricht, The Netherlands
3Department of Pathology, University of Limburg PO Box 616, 6200 MD, Maastricht, The Netherlands
4Department of Occupational and Environmental Health and Toxicology, University of Limburg P0 Box 616, 6200 MD, Maastricht, The Netherlands

5To whom all correspondence should be addressed

Groups of ten 5-week old male Wistar rats were fed a diet containing 0, 0.25, 0.50, 0.75, 1.0 or 2.0% butylated hydroxyanisole (BHA) ad libitum for 2 weeks; another group of rats served as a pair-fed control (PFC) group for the 2% BHA fed animals. Subsequently, rats were injected i.p. with the thymidine-analogue bromodeoxyundine (BrdU) which was incorporated into the DNA of cells during DNA synthesis. Cell kinetic parameters In gastro-intestinal tract tissues were determined by means of bivarixdate BrdU/DNA analysis applying flow-cytometry to randomized tissue samples or by applying immunohistology to randomized tissue sections. In the forestomach, glandular stomach, small intestineand colon/rectum, mean tissue labelling index (LI) was significantly Increased in rats on a diet supplemented with 2% BHA, in comparison with rats fed the basal diet (0% BHA) ad libitum or restricted to themean daily intake of 2% BRA-fed rats (PIFC). In the oesophagus of rats fed 2% BRA, the LI was significantly higher in comparison with their PFC group, but not with the group of rats fed 0% BHA ad libitum. In rat forestomach, an apparent no observed effect level for ad libitum fed rats was found at 0.5% BHA (LI) and at 0.75% BHA (potential doubling time). Thus, the oesophagus, glandular stomach, small intestine and large bowel, in addition to the forestomach, are possible target tissues in rats for the proliferation enhancing effects of BHA. At the timeof termination of the experiment, plasma BRA concentrations were dose dependently Increased and were In the range that is easily attained in man after ingestion of a dose equal to the acceptable daily intake for BRA (0.5 mg/kg).


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