Table 1.
Summary of the effect of DDT and DDE on oxidative phosphorylation.
| Purity | Model | Dose range | LOEL | Complex I | Complex II | Complex III | Complex IV | ATP synthase | Uncoupling | Morphological or structural changes | References |
|---|---|---|---|---|---|---|---|---|---|---|---|
| DDT | |||||||||||
| Not listed | Heavy beef heart mitochondria | ~2.5 umol/mga | ~2.5 umol/mg | 0–15% depression of oxidase activity by 1 umol in heavy heart beef mitochondria. | Reduction in succinate dehydrogenase enzymatic activity by 10–20% with 1 umol DDT in beef mitochondria. | — | — | — | — | — | (23) |
| >99% by gas-liquid chromatography | Rat liver mitochondria | 0, 50, 100, 150, 200 uM | 10 uM | X | 16% inhibition of succinate dehydrogenase with 50 uM. | 39% inhibition of succinate-cytochrome c reductase with 50 uM; 50 nmol/mg interferes with electron transfer between cytochromes b and c. | X | DDT inhibits ATPase by 38% with 200 uM in isolated mitochondria as measured by Ca2+ uptake driving by ATP hydrolysis. Inhibition starting around 10 uM. | Uncoupling observed with >200 uM in the presence of TMPD. | — | (24) |
| Not listed | Rat liver mitochondria | 0, 10, 20, 30, 40, 50 nmol DDT/mg | 20 nmol/mg | X | X | Inhibition of succinate cytochrome c reductase in isolated rat mitochondria after 20 nmol/mg; secondary effect on the ubiquinol-cytochrome c subunit. | X | Decrease in ATP synthesis at 3 nmol/mg. Increase in ATPase activity with ≥9.4 nmol/mg as measured by monitoring pH associated with ATP hydrolysis; inhibitory action at 19 nmol/mg on ATPase as measured by membrane potential. | X | Swelling observed above 50 nmol/mg. | (18) |
| >99% as tested by gc and hplc | Rat submitochondria | 30 ug/ml | 31 ug/ml | — | — | — | — | DDT inhibited ATPase activity by 29.4%. | — | — | (19) |
| >99% as tested by gc and hplc | Rat liver mitochondria | 0, 4, 8, 20 ug/ml | 4 ug/ml | — | — | — | — | Increase of latent ATPase activity at all doses. | Uncoupling observed with stimulation of State 4 respiration around 10 ug/ml. | Mitochondrial Swelling observed with 10 and 20 ug/ml. | (19) |
| Analytical grade | Rat liver mitochondria | 0, 50, 200, 600 mg/kg | 600 mg/kg | — | — | — | — | Increase in ATPase activity in rat liver and brain mitochondria by 600 mg/kg. | — | — | (21) |
| References in agreement | 2/3 | 2/3 | 2/2 | 2/2 | Conflicting agreement | 2/3 | 2/2 | ||||
| Evidence determination | Equivocal evidence–additional species needed | Equivocal evidence–additional species needed | Strong evidence that implicates transfer from Complex II | No evidence of effect | Strong evidence in a sensitive system | Equivocal evidence; unrealistic conditions | Strong evidence; unrealistic conditions | ||||
| DDE | |||||||||||
| Not listed | Heavy beef heart mitochondria | ~2.5 umol/mg | ~2.5 umol/mg | 5–20% depression of oxidase activity by 1 umol in heavy heart beef mitochondria. | Reduction in succinoxidase enzymatic activity by 5–15% with 1 umol DDE in beef mitochondria. | — | — | — | — | — | (23) |
| >99% as tested by gc and hplc | Rat Submitochondria | 30 ug/ml | 30 ug/ml | — | — | — | — | DDE inhibited ATPase activity by 32.4%. | — | — | (19) |
| >99% as tested by gc and hplc | Rat liver mitochondria | 0, 4, 8, 20 ug/ml | 4 ug/ml | — | — | — | — | Increase of latent ATPase activity at all doses. | Uncoupling observed with stimulation of State 4 respiration around 10 ug/ml. | Mitochondrial Swelling observed with 10 and 20 ug/ml. | (19) |
| Chromatographic grade | Rat liver mitochondria | 0, 20, 30 40, 50, 80, 100 nmol/mg protein | 50 nmol/mg | X | Succinate dehydrogenase and succinate cytochrome c reductase were partially inhibited with 50 nmol DDE/mg. | X | X | ATPase activity is inhibited at does below 50 nmol/mg when succinate is present. DDE stimulated ATPase in the presence of an uncoupler only at high concentrations (80 nmol/DDE/mg protein). | >80 nmol/mg increased permeability to protons, uncoupling oxidation from phosphorylation. | Mitochondrial Swelling observed with 80 nmol DDE/mg. | (20) |
| References in agreement | 0/2 | 2/2 | 1/1 | 1/1 | Conflicting agreement | 2/2 | 2/2 | ||||
| Evidence determination | Equivocal evidence–additional species needed | Strong evidence | No evidence of effect | No evidence of effect | Strong evidence in a sensitive system | Strong evidence; unrealistic conditions | Strong evidence; unrealistic conditions | ||||
a
Approximate values based on a range of 0.36–0.42 mg of protein for 1 umol of DDT; X indicate no significant effect reported; — indicate complex not studied.