The Journal of Nutrition
Biochemical, Molecular, and Genetic Mechanisms
Zinc Deficiency Affects DNA Damage, Oxidative
Stress, Antioxidant Defenses, and DNA Repair
Yang Song,4Scott W. Leonard,5Maret G. Traber,4,5and Emily Ho4,5*
4Department of Nutrition and Exercise Science and5Linus Pauling Institute, Oregon State University, Corvallis, OR 97331
Approximately 12% of Americans do not consume the Estimated Average Requirement for zinc and could be at risk for
marginal zinc deficiency. Zinc is an essential component of numerous proteins involved in the defense against oxidative
stress and DNA damage repair. Studies in vitro have shown that zinc depletion causes DNA damage. We hypothesized
that zinc deficiency in vivo causes DNA damage through increases in oxidative stress and impairments in DNA repair.
Sprague-Dawley rats were fed zinc-adequate (ZA; 30 mg Zn/kg) or severely zinc-deficient (ZD; ,1 mg Zn/kg) diets or were
pair-fed zinc-adequate diet to match the mean feed intake of ZD rats for 3 wk. After zinc depletion, rats were repleted with
a ZA diet for 10 d. In addition, zinc-adequate (MZA 30 mg Zn/kg) or marginally zinc-deficient (MZD; 6 mg Zn/kg) diets were
given to different groups of rats for 6 wk. Severe zinc depletion caused more DNA damage in peripheral blood cells than in
the ZA group and this was normalized by zinc repletion. We also detected impairments in DNA repair, such as
compromised p53 DNA binding and differential activation of the base excision repair proteins 8-oxoguanine glycosylase
and poly ADP ribose polymerase. Importantly, MZD rats also had more DNA damage and higher plasma F2-isoprostane
concentrations than MZA rats and had impairments in DNA repair functions. However, plasma antioxidant concentrations
and erythrocyte superoxide dismutase activity were not affected by zinc depletion. These results suggest interactions
among zinc deficiency, DNA integrity, oxidative stress, and DNA repair and suggested a role for zinc in maintaining DNA
integrity. J. Nutr. 139: 1626–1631, 2009.
Zinc deficiency is an important worldwide public health
problem with ~2 billion people who do not ingest adequate
amounts of zinc (1). Data from NHANES 2001–2002 show that
~12% Americans do not consume the Estimated Average
Requirement for zinc; thus, a large proportion of the U.S
population could be at risk for marginal zinc deficiency (2).
Epidemiological studies reveal associations between low circu-
lating zinc concentrations and increased risk of cancer (3,4).
However, the mechanisms by which zinc deficiency increase the
risk of cancer are still unclear and understudied. Zinc is an
important element in numerous proteins and plays a pivotal role
in several essential cell functions such as cell proliferation and
apoptosis, defense against free radicals, and DNA damage
repair. For instance, CuZn superoxide dismutase (SOD)6is an
important first-line defense enzyme against oxygen radical
species and p53 is an important zinc-containing transcription
factor that plays an essential role in the DNA damage response.
Low cellular zinc may increase oxidative stress, impair DNA
binding activity of p53, and interfere with its functions in DNA
repair (5,6). Thus, several different mechanisms may be involved
in processes leading to impaired DNA integrity with zinc
deficiency in vivo. Zinc deficiency may increase oxidative stress
that directly causes DNA damage and may impair DNA damage
repair responses (7).
Although increasing evidence suggests that zinc has antiox-
idant properties and protects tissue from oxidative damage (5,8–
15), many of these studies have only used severe zinc-depletion
protocols that obstruct growth and development and have little
physiological relevance in the general population. In contrast,
marginal zinc deficiency is more physiologically relevant to
1Supported by USDA2005-35200-15439, Oregon Agricultural Experiment Station
(OR00735),and the EnvironmentalHealthScienceCenteratOregonStateUniversity
(NIEHS P30 ES00210).
2Author disclosures: Y. Song, S. W. Leonard, M. G. Traber, and E. Ho, no
conflicts of interest.
3Supplemental Table 1 is available with the online posting of this paper at jn.
* To whom correspondence should be addressed. E-mail: emily.ho@oregonstate.
6Abbreviations used: AA, arachidonic acid; BER, base excision repair; FRAP,
ferric reducing ability of plasma assay; MZA, zinc-adequate group for marginal
zinc deficiency study; MZD, marginally zinc-deficient group; OGG1, 8-oxoguanine
glycosylase; PARP, poly ADP ribose polymerase; PF, pair-fed group; SOD,
superoxide dismutase; SSB, single-strand break; ZA, zinc-adequate group; ZD,
severely zinc-deficient group; ZnRe, zinc repletion group.
0022-3166/08 $8.00 ã 2009 American Society for Nutrition.
Manuscript received February 25, 2009. Initial review completed Mach 24, 2009. Revision accepted July 2, 2009.
First published online July 22, 2009; doi:10.3945/jn.109.106369.
human zinc deficiency (16), yet little is known about its effect on
oxidative stress and DNA damage.
Our current rat study examined the in vivo interactions
among zinc deficiency, DNA damage, oxidative stress, antiox-
idant defenses, and DNA repair in both severely and marginally
zinc-depleted rats. We hypothesized that alterations in zinc
status would affect DNA integrity by altering oxidative stress,
antioxidant defenses, and DNA repair functions. Previous
studies conducted in our laboratory have demonstrated that
severe zinc depletion increases oxidative stress biomarkers in rat
plasma (15). In the current study, we further assessed DNA
damage and DNA repair proteins in zinc-depleted rats and,
importantly, added a zinc repletion stage to test whether these
deleterious effects are reversible. Second, we used a physiolog-
ically relevant, marginally zinc-depleted rat model and investi-
gated the effects of marginal zinc deficiency on DNA integrity,
oxidative stress, and DNA repair. Therefore, our study is one of
the first to explore the effects of marginal zinc deficiency on
DNA integrity in vivo and may shed light on human trials
exploring the possible deleterious effects of marginal zinc
deficiency in humans.
Materials and Methods
Rats and diets. The rat protocol was approved by Oregon State
University’s (Corvallis, OR) Institutional Laboratory Animal Care and
Use Committee. Male Sprague-Dawley rats from Charles River were
acclimated for 1 wk to the temperature- and humidity-controlled
environment with a 12-h-dark/-light cycle. The rats for the severe zinc
deficiency study were maintained in stainless steel suspended cages and
the rats for the marginal zinc deficiency study were maintained in
polycarbonate cages. Diets were based on modified AIN-93G rodent
diets (17) for growing rats or AIN-93M diets (17) for sexually mature
rats, formulated with egg white rather than casein and with zinc
provided as zinc carbonate (Dyets). Deionized water was provided as
Severe zinc deficiency study. Rats (10/group, 3 wk old, ~50 g) were
randomly assigned to 3 dietary treatments: zinc-adequate diet (ZA
group; 30 mg Zn/kg), severely zinc-deficient diet (ZD group; ,1 mg Zn/
kg), or pair-fed zinc-adequate diet (PF group; 30 mg Zn/kg) to match the
mean feed intake in the ZD rats. Ten rats fed the ZD diet for 21 d were
switched to the zinc-adequate diet for up to 10 d for the zinc repletion
group (ZnRe). Diet intakes and body weights were measured daily. Rats
were killed following anesthesia with isoflurane overdose (1–5%; Henry
Marginal zinc deficiency study. Rats (12/group, 5 wk old, ~110 g)
were randomly assigned to 1 of 2 dietary treatments: zinc-adequate diet
(MZA group; 30 mg Zn/kg) or marginally zinc-deficient diet (MZD
group; 6 mg Zn/kg) for 42 d. Diet intakes and body weights were
measured twice every week. Rats were killed following anesthesia with
isoflurane overdose (1–5%; Henry Schein).
Tissue and blood collection. Blood samples were collected by cardiac
puncture into trace element-free vials containing EDTA. Plasma and
erythrocytes was separated immediately and frozen at 2808C until
analysis. Samples of liver were dissected and immediately snap frozen at
2808C until analysis.
Zinc analysis. Zinc concentrations were measured by inductively
coupled plasma-optical emission spectrometry (Teledyne Leeman Labs)
as described previously (15,18).
DNA damage. Single-strand breaks (SSB) in peripheral blood cells were
determined by alkali single-cell gel electrophoresis (Comet assay) as
described by Singh et al. (19). Images of 100 randomly selected nuclei
from each rat were analyzed for tail moments. Results are presented as
the fold of the tail moments of the ZA or MZA group.
Oxidative stress. Plasma F2-isoprostanes were measured as an index of
lipid peroxidation and indicator of oxidative stress in vivo. The sum of
various F2-isoprostanes with the appropriate mass:charge ratio and
fragmentation characteristics and arachidonic acid (AA) were measured
in plasma as previously described (20) using HPLC (Shimadzu HPLC
system) and multiple reaction monitoring on an Applied Biosystems/
MDS Sciex API 3000 triple quadrupole mass spectrometer.
Total antioxidant capacity. The ferric reducing ability of plasma
(FRAP) was measured at 550 nm on a microplate reader (Spectramax
190; Molecular Devices) as previously described (21). Plasma a-
tocopherol and ascorbic concentrations were measured by HPLC-ECD
as described (22–24).
Erythrocyte SOD activity. SOD activity was determined by the
xanthine oxidase-cytochrome c method according to McCord and
Fridovich (25) and L’Abbe ´ et al. (26). Hemoglobin concentration in cell
lysates was measured by Drabkin’s method (27).
Western analysis of DNA repair proteins. Proteins (30 mg/lane) were
separated by SDS-PAGE on a 4–12% bis-Tris gel (Invitrogen) and
transferred to nitrocellulose membrane (Bio-Rad). The primary anti-
bodies used for detection were mouse anti-p53 (Calbiochem), mouse
anti-poly ADP ribose polymerase (PARP; BD pharmingen), rabbit anti-
8-oxoguanine glycosylase (OGG1; Novus Biologicals), and mouse
anti-b-actin (Sigma). Bound antibodies were detected using either
goat anti-mouse IgG-horseradish peroxidase or goat anti-rabbit IgG-
horseradish peroxidase (Santa Cruz Biotechnology) and developed
with SuperSignal West Femto chemiluminescent substrate (Pierce).
Images were acquired on an Alpha Innotech photodocumentation
system and analyzed using Image J 1.37v software (NIH).
Electrophoretic mobility shift assay. p53 DNA binding activity was
assessed by electrophoretic mobility shift assay using the p53 IRDye 700
Infrared Dye Labeled Oligonucleotides (LiCOR Biosciences) as previ-
ously described (28). Briefly, nuclear extract were mixed with p53 oligo
IRDye 700. Infrared Dye was incubated at room temperature for 30 min.
For specific competitor reactions, the sample was incubated with
unlabeled p53 oligo before the addition of 50 fmol of labeled probe.
Reaction mixture was separated on a 6% acrylamide gel imaged and
Statistical analysis. Statistical analysis was performed with the use of
PRISM (version 4.0; GraphPad Software). One-way ANOVAwere used
for comparisons among the 4 dietary treatments with Tukey’s post hoc
test whenappropriate.Student’st test was usedfor comparisons between
MZD and MZA groups. Equal variances among groups were tested by
Bartlett’s test and logarithmic data transformation was performed in
cases of unequal variance. Differences were considered significant at P ,
0.05. All data are reported as mean 6 SEM unless otherwise indicated.
Body and organ weights.
Severe dietary zinc restriction (,1 mg Zn/kg) resulted in
anorexia and lower growth rates in the ZD rats than in the
ZA and PF rats (data not shown), which also differed from one
another. In addition, the ZD rats exhibited other signs of zinc
deficiency, including loss of hair, decreased activity, and
increased agitation. At the end of zinc depletion, body weights
in ZD rats (110.8 6 3.5 g) were less than in PF rats (136.6 6 2.3
g), which were less than in ZA rats (226.8 6 7.5 g) (P , 0.05).
Liver and spleen weights similarly differed among all 3 groups
(P , 0.05; data not shown). Repletion of the ZD rats with zinc-
adequate diet for 10 d partially restored body weight in the
Zinc, oxidative stress, and DNA damage1627
ZnRe group (202.0 6 4.9 g), but it remained 31.7% lower than
in the ZA group (291.6 6 10.0 g) (P , 0.05). However, the
growth rate during zinc repletion (9.41 6 0.33 g body weight/d)
was .8.5 times that during zinc depletion (1.08 6 0.04 g body
weight/d) (P , 0.05) and significantly greater than the growth
rate of the ZA group (7.20 6 0.32 g/d) (P , 0.05). Liver and
spleen weights were also restored by zinc repletion (data not
shown). Marginal zinc depletion also did not affect body and
organ weights, as expected. At the end of the study, the body
weight was 360.3 6 12.8 g in the MZA group and 380.6 6 8.4 g
in the MZD group.
Tissue zinc concentrations.
Hepatic zinc concentrations were lower in the ZD rats (0.53 6
0.03 mmol/g) than in the ZA rats (0.79 6 0.09 mmol/g) (P ,
0.001) and tended to be lower than in the PF rats (0.64 6 0.03
mmol/g) (P = 0.07). Hepatic zinc concentrations also differed
between ZA and PF rats (P , 0.05). These data in combination
with the physiological alterations in the ZD rats confirmed that
the rats fed the severely zinc-deficient diet developed zinc
deficiency. The 10-d zinc repletion period increased hepatic zinc
concentrations in the ZnRe rats (0.72 6 0.03 mmol/g) to the
control levels, suggesting that the rats achieved zinc-adequate
status following the repletion period. The MZD rats also had
lower hepatic zinc concentrations (0.66 6 0.03 mmol/g) than the
MZA rats (0.75 6 0.02 mmol/g) (P , 0.05), confirming altered
zinc status in the marginal zinc depletion model.
DNA damage in peripheral blood cells.
The mean tail moment of the ZD group was 1.3-fold that of the
PF rats (Fig. 1) (P , 0.05), indicating an increase in SSB with
severe zinc deficiency. The tail moment of the PF group did not
differ from the ZA group. The 10-d zinc repletion reduced the
tail moment to that of the PF and ZA controls, suggesting that
DNA damage was reversible with zinc repletion.
The mean tail moment of the MZD group was 1.2-fold that
of the MZA group (P , 0.05), indicating that marginal zinc
deficiency is sufficient to significantly increase DNA damage
(data not shown).
Oxidative stress in plasma.
Plasma AA concentrations, the precursor of F2-isoprostanes, a
biomarker for oxidative stress, were significantly lower in the
ZD rats and their PF rat controls than in the ZA rats (P , 0.05;
data not shown). When plasma F2-isoprostane concentrations
were normalized to AA concentrations, the concentrations of
plasma 15-series and 5-series F2-isoprostanes were greater in the
ZD group than in the ZA groups (Fig. 2A,B; P , 0.05). After
zinc repletion, the concentrations of plasma F2-isoprostanes did
not differ between the ZnRe and ZA groups (Fig. 2A,B; P .
0.05). However, plasma F2-isoprostanes did not differ between
the PF and ZD groups. It is likely that the severe food restriction
in itself is a marked stress on the rats that could induce high
oxidative stress (Fig. 3A); at the end of zinc depletion on d 20,
feed intake in the PF group was 47% of that of the ZA group.
Another possible explanation is that food restriction resulted in
low zinc intake in the PF rats (Fig. 3B); at the end of zinc
depletion on d 20, zinc intakein the PFgroup was 46%of that of
the ZA group. This restricted zinc intake may effectively cause a
marginal zinc deficiency. Because the hepatic zinc concentrations
were 20% lower in the PF (0.64 6 0.03 mmol/g) than in the ZA
groups (0.79 6 0.09 mmol/g) (P , 0.05), it further supports the
concept that zinc status was compromised in the PF rats.
Importantly, the MZD rats also had higher plasma 15- and
5-series F2-isoprostane concentrations (15-series F2-isoPs, 5.23 6
0.29 pg/mg AA; 5-series F2-isoPs, 10.07 6 0.78 pg/g AA) than
the MZA rats (15-series F2-isoPs, 4.06 6 0.24 pg/mg AA;
5-series F2-isoPs, 7.21 6 0.40 pg/mg AA) (P , 0.01), yet plasma
AA concentrations were not affected by marginal zinc depletion
(data not shown).
FRAP, vitamin C, vitamin E, and erythrocyte SOD. The ZD
group had lower plasma FRAP values and AA and a-tocopherol
concentrations than the ZA group (P , 0.05) but not compared
with the PF group; dietary zinc repletion restored these to
control levels (Table 1). Hepatic a-tocopherol concentrations in
the ZD group were lower than in the ZA and PF groups (Table 1;
P , 0.05), similar to our previous findings (15).
Antioxidant status did not differ between the MZD and
MZA groups (Supplemental Table 1), suggesting that antioxi-
peripheral blood cells. Values are means 6 SEM, n = 10. Means
without a common letter differ, P , 0.05.
Effects of dietary zinc status on DNA SSB in rat
isoprostanes (IsoP) (A) and 5 series F2-isoprostanes (B) in rats. Values
are means 6 SEM, n = 10. Means without a common letter differ, P ,
Effects of dietary zinc status on plasma 15 series F2-
1628Song et al.
dant defenses are inadequate to prevent the oxidative stress and
DNA damage due to marginal zinc deficiency.
Erythrocyte SOD is comprised of cytosolic CuZnSOD, an
important zinc-containing antioxidant defense enzyme in the
circulation. Erythrocyte SOD activities were not altered with
either severe (Table 1) or marginal zinc deficiencies (Supple-
mental Table 1).
Zinc-containing DNA repair proteins in livers. Hepatic
OGG1 protein levels were substantially higher in the ZD group
than in the ZA and PF groups, which did not differ from one
another (Fig. 4A;P ,0.05). Zinc repletion reduced OGG1levels
in the ZnRe group did not differ from the ZA and PF groups.
The MZD group also had higher OGG1 protein levels than the
MZA group (Fig. 4D; P , 0.05). However, hepatic PARP
protein levels did not differ among the ZD, ZA, PF, and ZnRe
groups (Fig. 4B) or between the MZD and MZA groups (Fig.
The ZD group had higher p53 protein levels in livers than the
PF and ZA groups (Fig. 4C; P , 0.05) and zinc repletion reduced
p53 protein to control levels. However, DNA binding activity of
p53 in liver nuclear extract was unchanged (data not shown),
suggesting the functional activity of p53 might be compromised.
The MZD group did not have altered p53 protein levels in liver
(Fig. 4F) and DNA binding activity of p53 was unchanged (data
not shown), despite this group having more DNA damage than
the MZD group. Therefore, DNA repair pathways may be
impaired with severe and marginal zinc deficiencies.
This study shows that both severe and marginal zinc deficiencies
in vivo increase oxidative stress, impair DNA integrity, and
increase DNA damage in rat peripheral blood cells. Concom-
itant with increases in DNA damage are impaired DNA repair
functions with zinc deficiency. Importantly, DNA damage and
oxidative stress biomarkers are reversed upon zinc repletion.
This study highlights the importance of zinc in the maintenance
of DNA integrity and points out that even marginal zinc
deficiency has deleterious consequences and may increase the
risk for DNA damage.
The mechanisms by which zinc deficiency affects DNA
damage are unclear. We have previously postulated that
increased DNA damage with zinc deficiency is a multi-factorial
process involving both perturbations in oxidative stress and
compromised DNA repair (7). Perturbations in oxidative stress
with zinc deficiency may be attributed to the antioxidant
functions of zinc; however, the mechanisms by which zinc
protects macromolecules from oxidative modification are not
completely understood. The current study shows that in the
(FRAP, ascorbic acid, and a-tocopherol) and erythrocyte SOD
activity are not directly affected by dietary zinc. However, unlike
plasma a-tocopherol, hepatic a-tocopherol levels were reduced
with zinc depletion. On the other hand, plasma F2-isoprostanes
levels, an index of lipid peroxidation, were the same in the ZD
andPFrats. It is possible thatthe vitaminE status inthe liverwas
compromised to maintain plasma a-tocopherol levels and thus
suppresses lipid peroxidation caused by zinc depletion. How-
ever, further studies are required to confirm the effects of zinc
deficiency on the metabolism and transportation of hepatic
Although zinc may not regulate antioxidant defenses directly,
several other mechanisms could be involved in the antioxidant
activity of zinc. First, zinc protects sulfhydryl groups in proteins
from oxidation and helps maintain normal functions of proteins
(29). Zinc may modulate the oxido-reductive environment in
cells through modulation of thiol status. Thus, zinc depletion in
vivo may change the intracellular environment from a reductive
to a more oxidative state (13,30–32) and make cells vulnerable
to oxidative stress. Second, zinc antagonizes the activities of
bivalent transition metals, including iron and copper, and
intake (B) in rats fed a ZD, PF, or ZA diet for 21 d, and in ZnRe rats fed
a ZD diet for 21 d and then a ZA diet for 10 d. Values are means 6
SEM, n = 10. *ZA differs from all other groups, P , 0.05. #PF differs
from the ZD and ZnRe, P , 0.05.
Effect of dietary zinc status on feed intake (A) and zinc
Plasma and tissue antioxidant status in rats fed a ZD, PF, or ZA diet for 21 d and in ZnRe
rats fed a ZD diet for 21 d and then a ZA diet for 10 d1
79.3 6 7.8a
31.4 6 2.8b
28.3 6 3.7b
75.0 6 7.0a
nmol/g U/mg Hb2
100.1 6 4.2
101.7 6 4.1
105.1 6 4.2
89.0 6 6.6
247.0 6 21.8a
169.2 6 5.8b
160.9 6 5.1b
258.9 6 9.6a
18.8 6 1.0a
13.0 6 0.9b
14.0 6 0.9b
20.7 6 0.7a
127.1 6 12.2a
58.1 6 6.9c
90.8 6 9.8b
100.7 6 5.6a,b
1Values are means 6 SEM, n = 10. Means in a column with superscripts without a common letter differ, P , 0.05.
Zinc, oxidative stress, and DNA damage1629
prevents the deleterious free-radical reactions (e.g. Fenton
reaction) stimulated by iron and copper. Third, zinc is a
component of metallothioneins that are part of classic antiox-
idant defenses. Metallothionein levels are decreased by zinc
deficiency in liver and esophagus (33,34). Our laboratory has
also detected a decrease in prostate metallothionein expression
with zinc deficiency in rats (M. Yan and E. Ho, unpublished
data). A lack of metallothionein may further sensitize cells to
oxidative insults. Further exploration of these potential mech-
anisms is an important area of future research.
Increases in DNA damage with zinc deficiency may not be
due only to perturbations in oxidative stress but also to
compromised DNA repair functions. In the current study,
repletion of zinc deficiency reversed DNA damage in peripheral
blood cells containing both short-lived neutrophils and long-
lived lymphocytes, suggesting that DNA damage is repaired in
long-lived cells and/or eliminated with damaged cells through
cell death or cell apoptosis. Normally, accumulation of DNA
damage stimulates cell responses, including DNA repair, cell
cycle arrest, and apoptosis, which help repair DNA damage and
inhibit the accumulation of mutations. However, in zinc-
deficient rats, DNA damage responses may be compromised,
which causes the accumulation of DNA damage and possible
increases in cancer risk.
Different mechanisms could be involved in altering DNA
damage responses in zinc-deficient rats. Loss of intracellular zinc
may decrease the expression or impair the function of DNA
repair proteins, thereby interrupting DNA repair pathways. For
example, p53 is a zinc-containing protein that plays an essential
role in regulating DNA repair, cell proliferation, and cell death
(35). Zinc is located in the DNA binding domain and is essential
for the DNA binding activity of p53. p53 expression is induced
in zinc-depleted cells and rats (5,35,36). However, the current
study and our previous in vitro studies (28,36) show that the
DNA binding activity of p53 is impaired by zinc deficiency. The
current study also assessed 2 other DNA repair proteins, PARP
and OGG1, which play pivotal roles in the base excision repair
(BER) pathway. 8-Hydroxyl-29-deoxyguanosine is a biomarker
for oxidative DNA damage and is one of the major targets of
BER. OGG1 functions in the first step of the BER pathway to
recognize and remove 8-hydroxyl-29-deoxyguanosine (37).
PARP binds to DNA SSB created by OGG1 through its zinc
finger motif and recruits other DNA repair factors (e.g. X-ray
repair cross complementing gene and DNA ligase) to the nick to
complete the whole repair process (38,39). Although both of
them have zinc-finger motifs, zinc status appears to affect their
expression differently. These results point out a potential
hierarchy of zinc-related protein function that may be preserved
in the absence of cellular zinc levels. This study shows that
OGG1 expression is dramatically increased by marginal and
severe zinc depletion, indicating increased oxidative DNA
damage with zinc deficiency. However, PARP capacity and
expression is decreased or only slightly altered with zinc
deficiency (40,41). This lack of response or negative response
of PARP to zinc depletion could markedly interrupt the overall
BER pathway and contribute to the accumulation of DNA
damage. Although marginal and severe zinc deficiency may
affect DNA repair proteins differently, overall, they both impair
DNA repair functions and disable cells to get rid of oxidative
In the United States, ~12% people do not consume enough
zinc (2). Infants, children, women, and elderly people are at high
risk of marginal zinc deficiency because of either high nutrient
requirements or compromised digestion and absorption func-
tions (42). This study confirms that zinc depletion, including
marginal zinc deficiency, promotes DNA damage. The impair-
ment of DNA integrity could have an important impact on
several processes involved in immune function, cancer, and other
degenerative disorders. However, these deleterious effects of zinc
deficiency on DNA integrity do appear to be reversible. The
results of this study suggest that there are complex in vivo
interactions among zinc deficiency, DNA integrity, oxidative
stress, and DNA repair and suggest a role for zinc in maintaining
status on the protein levels of DNA
repair proteins OGG1(A,D), PARP(B,
E), and p53(C,F) in rat livers. Repre-
sentative western blots are shown in
the inserts. Values are means 6 SEM,
n = 6. (A–C) Means without a com-
mon letter differ, P , 0.05. (D–F)
*Different from the MZA, P , 0.05.
Effects of dietary zinc
1630 Song et al.
Acknowledgment Download full-text
We thank Alan Taylor from Linus Pauling Institute at Oregon
State University for his assistance in conducting the oxidative
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