Effect of micelle fatty acid composition and 3,4,3 ',4 '-tetrachlorobiphenyl (TCB) exposure on intestinal [C-14]-TCB bioavailability and biotransformation in channel catfish in situ preparations
Am. Doi et al., Effect of micelle fatty acid composition and 3,4,3 ',4 '-tetrachlorobiphenyl (TCB) exposure on intestinal [C-14]-TCB bioavailability and biotransformation in channel catfish in situ preparations, TOXICOL SCI, 55(1), 2000, pp. 85-96
Polychlorinated biphenyls are transferred in the diet along aquatic food ch
ains. This study investigated the effect of dietary micelle composition and
3,4,3',4'-tetrachlorobiphenyl (TCB) exposure upon the subsequent systemic
bioavailability and intestinal metabolism of [C-14]-TCB in a catfish in sit
u intestinal preparation. Initial in vitro experiments examined the solubil
ity of [C-14]-TCB in micelles of varying fatty acid composition. Micelles c
omposed of single fatty acids demonstrated greater [C-14]-TCB solubility wi
th those fatty acids of longer chain length. Similarly, micelles of the lon
g-chain fatty acid, linoleic acid, solubilized more [C-14]-TCB than mixed m
icelles formulated from equal amounts of myristic (14:0), palmitic (16:0),
stearic (18:0), or linoleic (18:2) acids. Systemic bioavailability of [C-14
]-TCB (60 mu M) from an in situ perfused intestinal preparation was 2.2-fol
d greater when delivered to the intestine in linoleic acid micelles as comp
ared to the mixed micelle preparation. Catfish exposed in vivo to either 0.
5 or 5.0 mg TCB/kg feed for 10 days resulted in a 45 to 47% decrease in the
subsequent systemic bioavailability of [C-14]-TCB in the in situ intestina
l preparation. Total intestinal cytochrome P450 content was not significant
ly affected by TCB preexposure. Immunodetectable CYP1A was found only in th
e 5.0 mg TCB/kg diet treatment. Corresponding intestinal aryl hydrocarbon h
ydroxylase (AHH) activities were 2.46 +/- 1.16, 2.43 +/- 1.58, and 11.35 +/
- 10.25 pmol/min/mg protein for the control, 0.5, and 5 mg TCB/kg diet grou
ps, respectively. [C-14]-TCB in the in situ preparation was metabolized to
only a small degree upon a single pass through the intestinal mucosa of the
catfish. High variability and low rates of metabolism precluded the associ
ation of the magnitude of metabolism with dietary TCB pretreatment. Analysi
s of tissue sample extracts demonstrated 4 minor peaks, 3 of which were ten
tatively identified by co-elution with standards as 2-OH-3,4,3',4'-TCB, 4-O
H-3,5,3',4'-TCB, and 5-OH-3,4,3',4'-TCB. A fourth remains unidentified. His
tological changes in the intestine such as thinning of the submucosa and in
creased numbers of goblet cells were evident at the 5.0 mg TCB/kg diet dose
. These results suggest that TCB intestinal bioavailability may be linked t
o micelle composition as well as TCB exposure history. Furthermore, single
pass intestinal metabolism appears to be a minor contributor to the biotran
sformational modification of dietary TCB.