Dose-dependent effects of short-term dietary administration of the food additive butylated hydroxyanisole on cell kinetic parameters in rat gastro-intestinal tract.
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 bromodeoxyuridine (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 bivariate BrdU/DNA analysis applying flow-cytometry to randomized tissue samples or by applying immunohistology to randomized tissue sections. In the forestomach, glandular stomach, small intestine and 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 the mean daily intake of 2% BHA-fed rats (PFC). In the oesophagus of rats fed 2% BHA, 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 time of termination of the experiment, plasma BHA 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 BHA (0.5 mg/kg).
Department of Human Biology, University of Limburg, Maastricht, The Netherlands.
H
H
Verhagen
C
C
Furnée
B
B
Schutte
F T
FT
Bosman
G H
GH
Blijham
P T
PT
Henderson
F
F
ten Hoor
J C
JC
Kleinjans
D000818:Animals; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects; D004032:Diet; D004064:Digestive System / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008940:Mitotic Index / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000166:cytology / Q000187:drug effects; D012016:Reference Values; D013270:Stomach / Q000166:cytology / Q000187:drug effects
D002083:Butylated Hydroxyanisole