Differences in tryptophan binding to hepatic nuclei of NZBWF1and Swiss mice : Insight into mechanism of tryptophan's effects

We have observed that in NZBWF 1 mice the affinity for L-tryptophan binding to hepatic nuclei in vitro is markedly less than that of Swiss mice. In vitro binding of [ 3 H]tryptophan to hepatic nuclei from both strains was determined without and with unlabeled L-tryptophan(10 -4 mol/L). The relative specific binding of L-tryptophan to hepatic nuclei in vitro was 60.9 ± 4.4% for Swiss mice and 35.8 ± 5.4% (P < 0.01) in NZBWF 1 mice. The total specific binding (bound radioactivity/mg nuclear protein) of L-tryptophan to hepatic nuclei in vitro was 74.9% (P < 0.05) lower in NZBWF 1 mice than in Swiss mice. Other strains (DBA, SJL and BALB/c) had specific binding affinities similar to that of Swiss mice. Serum and hepatic free tryptophan concentrations and hepatic tryptophan dioxygenase activity in mice that were food-deprived ovemight or 1 h after tube-feeding L-tryptophan (20 mg/100 g body weight) were similar in the strains of mice. In vitro [ 14 C] leucine incorporation into protein using hepatic microsomes of mice 1 h after tube-feeding L-tryptophan (20 mg/100 g body weight) revealed a significantly greater (P < 0.05) increase relative to food-deprived controls in Swiss mice (76.8 ± 19.2%) than the increase in NZBWF 1 mice (26.5 ± 2.6%). Nuclear [ 14 C]-labeled RNA release in vitro was increased 77.2 ± 18.0% by tube-feeding of L-tryptophan in Swiss but only 7.6 ± 5.8% (P < 0.02) in NZBWF 1 mice. Liver nuclear poly(A)-polymerase and nucleoside triphosphatase activities were variably increased by the administration of L-tryptophan in both strains. In summary, compared with Swiss mice, NZBWF 1 mice have a lower specific binding affinity for L-tryptophan by hepatic nuclei, and this alteration may account for the other differences in responses to L-tryptophan by the two strains.