TABLE 3.
Effects of diet on folate, uracil, uridine, thymidine, and deoxyuridine concentrations by maternal genotype1
| Diet and maternal genotype | Folate,2 fmol/μL | Thymidine,3 μmol/L | Uridine,4 μmol/L | Deoxyuridine,5 μmol/L | Uracil,6 pg/μg DNA |
| C | 165.12 ± 12.30 (FD*) | 1.28 ± 0.23 | 8.17 ± 1.24 | 1.55 ± 0.16 | 0.23 ± 0.03 |
| Shmt1+/+ | 170.79 ± 9.32 | 1.43 ± 0.31 | 7.87 ± 1.60 | 1.60 ± 0.22 | 0.23 ± 0.04 |
| Shmt1−/− | 159.45 ± 24.03 | 1.03 ± 0.33 | 8.58 ± 2.11 | 1.45 ± 0.12 | 0.24 ± 0.03 |
| C+T | 260.07 ± 26.54 (C*) | 1.02 ± 0.10 | 9.88 ± 1.25 | 2.10 ± 0.09 | 0.21 ± 0.02 |
| Shmt1+/+ | 263.51 ± 50.54 | 1.25 ± 0.14 | 11.35 ± 1.39 | 1.97 ± 0.13 | 0.21 ± 0.02 |
| Shmt1−/− | 258.01 ± 34.69 | 0.82 ± 0.07 | 8.13 ± 2.09 | 2.22 ± 0.12 | 0.21 ± 0.03 |
| C+U | 163.25 ± 19.86 | 1.01 ± 0.09 | 5.70 ± 0.54 | 1.51 ± 0.12 | 0.18 ± 0.01 |
| Shmt1+/+ | 180.48 ± 27.74 | 0.78 ± 0.02 | 5.56 ± 0.87 | 1.54 ± 0.12 | 0.17 ± 0.01 |
| Shmt1−/− | 146.02 ± 29.27 | 1.24 ± 0.08 | 5.81 ± 0.74 | 1.48 ± 0.22 | 0.20 ± 0.03 |
| C+dU | 261.21 ± 19.93 (C*) | 1.12 ± 0.11 | 5.27 ± 1.02 | 2.55 ± 0.32 | 0.19 ± 0.01 |
| Shmt1+/+ | 272.29 ± 27.65 | 1.13 ± 0.15 | 5.91 ± 1.49 | 2.10 ± 0.22 | 0.18 ± 0.01 |
| Shmt1−/− | 253.30 ± 29.31 | 1.09 ± 0.08 | 3.98 ± 0.65 | 3.45 ± 0.68 (C*) | 0.19 ± 0.02 |
| FD | <10 (C*) | 0.89 ± 0.12 | 4.86 ± 0.32 | 1.66 ± 0.09 | 0.20 ± 0.03 |
| Shmt1+/+ | <10 | 0.73 ± 0.06 | 4.87 ± 0.38 | 1.54 ± 0.12 | 0.18 ± 0.02 |
| Shmt1−/− | <10 | 1.04 ± 0.24 | 4.84 ± 0.58 | 1.77 ± 0.12 | 0.24 ± 0.07 |
| FD+T | <10 | 1.36 ± 0.44 | 10.42 ± 1.79 (*FD) | 1.75 ± 0.25 | 0.20 ± 0.02 |
| Shmt1+/+ | <10 | 0.79 ± 0.16 | 11.20 ± 3.03 | 1.67 ± 0.58 | 0.16 ± 0.01 |
| Shmt1−/− | <10 | 1.82 ± 0.75 | 9.80 ± 2.42 | 1.82 ± 0.17 | 0.26 ± 0.02 |
| FD+U | <10 | 0.85 ± 0.05 | 8.82 ± 1.59 | 1.52 ± 0.16 | 0.22 ± 0.02 |
| Shmt1+/+ | <10 | 0.85 ± 0.06 | 13.22 ± 2.36 | 1.89 ± 0.27 | 0.20 ± 0.03 |
| Shmt1−/− | <10 | 0.85 ± 0.08 | 5.52 ± 1.26 | 1.24 ± 0.15 | 0.23 ± 0.02 |
| FD+dU | <10 | 1.10 ± 0.16 | 8.61 ± 0.92 | 1.95 ± 0.19 | 0.19 ± 0.01 |
| Shmt1+/+ | <10 | 1.15 ± 0.13 | 8.69 ± 1.39 | 1.62 ± 0.23 | 0.17 ± 0.01 |
| Shmt1−/− | <10 | 1.07 ± 0.28 | 8.53 ± 1.33 | 2.24 ± 0.27 | 0.22 ± 0.01 |
Values are means ± SEs from univariate descriptive statistics. General linear models were used to examine the effect of maternal diet, maternal Shmt1 genotype, and the interaction between diet and maternal genotype on folate, uracil, uridine, thymidine, and deoxyuridine concentrations. A set of a priori comparisons between diets was assessed (C+T, C+U, and C+dU vs. C; FD vs. C; FD+T, FD+U, and FD+dU vs. FD) for folate, uracil, uridine, and thymidine concentrations, and a Bonferroni correction was applied. *Significant comparisons are preceded by the diet of comparison, P < 0.05. C, control diet; C+dU, control diet supplemented with 2′-deoxyuridine; C+T, control diet supplemented with thymidine; C+U, control diet supplemented with uridine; FD, AIN-93G lacking folic acid; FD+dU, folate-deficient diet supplemented with 2′-deoxyuridine; FD+T, folate-deficient diet supplemented with thymidine; FD+U, folate-deficient diet supplemented with uridine.
There was a significant effect of diet on folate concentrations (P < 0.0001). The effect of maternal genotype (P = 0.3622) on folate concentrations and the interaction between diet and maternal genotype (P > 0.05) were not significant. All folate-deficient diets had folate concentrations <10 fmol/μL. *The FD diet had significantly lower folate concentrations than the C diet (unadjusted P < 0.0001, adjusted P < 0.0007). The C+T diet and the C+dU diet had significantly higher folate concentrations than the C diet (C+T vs. C: unadjusted P < 0.0001, adjusted P < 0.0007; C+dU vs. C: unadjusted P < 0.0001, adjusted P < 0.0007).
There were no significant effects of diet (P > 0.05) or maternal genotype (P > 0.05) on plasma thymidine concentrations. The interaction between diet and maternal genotype was not significant (P > 0.05).
There was a significant effect of diet (P = 0.0022) and maternal genotype (P = 0.0397) on plasma uridine concentration. The interaction between diet and maternal genotype was not significant (P > 0.05). *The FD+T diet had significantly higher uridine concentrations than the FD diet (unadjusted P = 0.0014, adjusted P = 0.0098). The FD+U and FD+dU diets also had higher uridine concentrations than the FD diet, although this was not statistically significant after adjusting for multiple comparisons (FD+U vs. FD: unadjusted P = 0.0085, adjusted P = 0.0595; FD+dU vs. FD: unadjusted P = 0.0124, adjusted P > 0.05).
There was a significant effect of diet (P < 0.0001) on deoxyuridine concentrations. There was no significant effect of maternal genotype on deoxyuridine concentrations (P = 0.0836). However, the interaction between diet and maternal genotype was significant [F(7, 72) = 2.88; P = 0.0096]. *The C+dU diet had significantly higher deoxyuridine concentrations than the C diet in the Shmt1−/− maternal genotype (unadjusted P < 0.0001, adjusted P < 0.0007), although there were no significant differences in the Shmt1+/+ maternal genotype (unadjusted P = 0.0954, adjusted P > 0.05).
There was no significant effect of diet on uracil concentrations (P = 0.6). There was a significant effect of maternal genotype on uracil concentrations (P = 0.0135). The interaction between diet and maternal genotype was not significant (P > 0.05).