Application of a dynamic in vitro gastrointestinal tract model to study the availability of food mutagens, using heterocyclic aromatic amines as model compounds
C. Krul et al., Application of a dynamic in vitro gastrointestinal tract model to study the availability of food mutagens, using heterocyclic aromatic amines as model compounds, FOOD CHEM T, 38(9), 2000, pp. 783-792
The TNO gastro-Intestinal tract Model (TIM) is a dynamic computer-controlle
d in vitro system that mimics the human physiological conditions in the sto
mach and small intestine. In the current TIM physiological parameters such
as pH, temperature, peristaltic movements, secretion of digestion enzymes,
bile and pancreatic juices, and absorption of digested products-by removal
through dialysis-was simulated. Heterocyclic aromatic amines (HAA; viz. IQ,
MeIQ, MeIQx and PhIP) were used as model compounds for food mutagens, and
the passage through TIM was investigated for each of these compounds separa
tely. Subsequently, the influence of a matrix and different rates of passag
e on the availability for absorption and distribution were studied in exper
iments with prepared meat, supplemented with MeIQx. Samples taken at variou
s time points from the jejunal and ileal dialysates and from the lumen at t
he end of the small intestine (ileal delivery) were tested for the presence
of mutagenic activity in the Ames test with Salmonella typhimurium strain
TA98 as indicator, in the presence of mammalian metabolic activation (rat S
9 mix). The results show that, comparable with the human in vivo situation,
all four HAA are quickly removed (approx, 50% in 2 hr; approx. 95% in 6 hr
) and mainly recovered from the lumen into the jejunal and ileal dialysates
(94% of recovery). Only 5 +/- 1.5% is recovered in the chyme at the end of
the small intestine. When MeIQx was added to meat, its availability for ab
sorption was slower, although the influence of the gastrointestinal passage
time on the availability of MeIQx was more pronounced than this matrix eff
ect. More MeIQx was found in the jejunal dialysate (23%; P < 0.01) and less
in the ileal delivery (8%; P < 0.01) when simulating the gastrointestinal
passage of solid meals was compared to simulating that of liquid meals. The
present experiments demonstrate that TIM can be applied to study in vitro
the availability of heterocyclic aromatic amines in the gastrointestinal tr
act. More generally, these studies indicate that TIM shows promise as a use
ful tool for various research purposes dealing with the availability for ab
sorption of mutagenic as well as antimutagenic components in food. (C) 2000
Elsevier Science Ltd, All rights reserved.