Energy restriction and oxidative DNA damage in humans.
The cancer-preventive effect of energy restriction in rodents has been related to a decrease in oxidative damage to DNA. We have investigated the effect of energy restriction on the rate of oxidative DNA modification estimated from the urinary excretion of the repair product, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in healthy, normal weight men. Before and after 10 weeks on a diet containing 80 (n = 16) or 100% (n = 8) of the estimated weight-maintaining energy, resting metabolic rate (RMR) was measured and 24-h urine was collected for 8-oxodG determination by HPLC. During the study, the weight loss was 10 and 2.5% of the initial weight, mostly in terms of fat, and the RMR decreased by 13 and 8% in the energy-restricted and control groups, respectively. With the use of t tests there was no significant difference within or between groups with respect to 8-oxodG excretion. However, if RMR was included as a covariate in multifactorial ANOVA, an average relative 17% (2-31%; 95% confidence interval) increase in 8-oxodG excretion in the energy-restricted group was significantly different from the corresponding value of the control group (P < 0.02). In the energy-restricted group the change in 8-oxodG excretion was correlated closely with the decrease in RMR (r = 0.63; P = 0.013). In the present study, 20% energy restriction for 10 weeks did not reduce oxidative DNA damage; we question a beneficial effect on cancer risk in normal weight humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Loft
S
S
Department of Pharmacology, University of Copenhagen, Panum Institute, Denmark.
Velthuis-te Wierik
E J
EJ
van den Berg
H
H
Poulsen
H E
HE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000704:Analysis of Variance; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011897:Random Allocation; D015431:Weight Loss / Q000502:physiology*
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine