Journal of Cancer Therapy, 2013, 4, 1373-1381
http://dx.doi.org/10.4236/jct.2013.48163 Published Online October 2013 (http://www.scirp.org/journal/jct)
1373
Investigating Catalase and Carbonic Anhydrase Enzyme
Activities and Levels of Certain Trace Elements and
Heavy Metals in Patients with Primary and
Metastatic Hepatic Carcinoma
Ayse Arslan1*, Halit Demir1, Harun Arslan2
1Department of Biochemistry, Faculty of Science, Yuzuncu Yil University, Van, Turkey; 2Radiology Department, Van Regional
Training and Research Hospital, Van, Turkey.
Received September 19th, 2013; revised October 15th, 2013; accepted October 23rd, 2013
Copyright © 2013 Ayse Arslan et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Hepatocellular carcinoma (HCC) is among most common terminal cancer types in the world. Primary etiological factors
include cirrhosis, hepatitis, aflatoxin and alcohol. The current study was conducted to determine cytosolic erythrocyte
carbonic anhydrase and catalase enzyme activities and levels of some trace elements. For this purpose, 40 patients with
primary and metastatic hepatic cancer and 29 healthy volunteers enrolled to the study. Catalase and carbonic anhydrase
enzyme activities and serum trace element levels were measured in patient and control groups. In the current study,
serum copper, magnesium, manganese and zinc levels were lower in the primary and metastatic hepatic cancer group in
comparison with the control group (P < 0.05). In contrast, serum iron, cobalt, cadmium and lead levels were higher in
the patient relative to the control group (P < 0.05). In comparison with the control group, the catalase level was lower in
primary and metastatic cancer group, while the carbonic anhydrase level was higher in the cancer group (P < 0.05).
Changes in levels of trace elements and anti-oxidant enzymes may be the factors which influence the development and
progression of liver cancer. The carbonic anhydrase enzyme can be a useful indicator in the diagnosis of cancer.
However, this issue warrants further investigation.
Keywords: Primary and Metastatic Liver Cancer; Catalase; Carbonic Anhydrase; Trace Element; Heavy Metal
1. Introduction
Hepatic carcinoma is one of common solid cancers,
which leads to the death of 650,000 people per year
worldwide [1]. The most significant risk factor of hepatic
cancer is liver cirrhosis. It accounts for 90% of hepatic
carcinoma cases. In addition, important risk factors in-
clude chronic viral hepatic infections (HBV-Hepatitis B
and HCV-Hepatitis C), alcohol, aflatoxin, intoxications
and genetic diseases such as hemochromatosis and dia-
betes [1,2].
Hepatic tumors are divided into three groups, include-
ing primary benign, primary malignant and secondary
(metastatic) tumors. The ratio of primary and metastatic
tumor is 1/20. Primary hepatic cancers are usually di-
vided into two groups. If the tumor originates from
hepatocytes, it is referred to as hepatocellular carcinoma
(HCC), while the term is cholangiocellular carcinoma
(CCC) if it is derived from intra-hepatic bile ducts. HCC
accounts for 90% of primary hepatic carcinomas, while
CCC accounts for 10 percent of all liver cancer cases
[3,4].
Hydrogen peroxide (H2O2) is an oxidative agent,
which is, in fact, a byproduct of some physiological pro-
cesses, such as cellular respiration. Increases in oxidant
molecules can be suppressed by natural anti-oxidant sub-
stances, which are normally found at particular levels in
the body. Thus, the level of oxidants is balanced by the
suppressive effect of anti-oxidant substance in a healthy
organism [5]. Oxidative stress occurs if the sensitive
balance between free radicals and the anti-oxidant de-
fense mechanism is impaired and shifts in a manner fa-
voring pro-oxidant and oxidant substances. It was dem-
onstrated that oxidative stress causes tissue damage and
it plays a role in the development of pathological condi-
tions such as cancer, diabetes and atherosclerosis [6,7].
*Corresponding author.

Investigating Catalase and Carbonic Anhydrase Enzyme Activities and Levels of Certain Trace Elements
and Heavy Metals in Patients with Primary and Metastatic Hepatic Carcinoma
1374
Catalase (CAT; E.C. 1.11.1.6) is an enzyme, which plays
a role in oxidative stress by converting hydrogen perox-
ide to molecular oxygen (O2) and water (H2O). Catalase
activity is influenced by some physiological conditions
and particular diseases, including cancer [5]. A decrease
in the level of anti-oxidant substances may lead to cellu-
lar damage and malignant transformation, since the bal-
ance between pro-oxidant and anti-oxidant substances
will impair [8].
Carbonic anhydrase (CA; E.C. 4.2.1.1) is a family of
enzymes in the group of metallo-enzymes, which cata-
lyze the conversion between CO2 and 3 [9]. CAI
and CAII are two enzymes which are abundant in eryth-
rocytes, and in particularly, CAII has high activity [10].
Various studies had found that carbonic anhydrases play-
ed a role in malignant cerebral tumors and gastric and
pancreatic cancers [11]. In malignant diseases, acidic
extracellular fluid promotes the dissemination behavior
of tumor [12]. It was suggested that hydration of CO2
into H2CO2, which is reversibly catalyzed by carbonic
anhydrase iso-enzymes, plays a role in the acidity of ex-
tracellular fluid [13]. In the literature, there is no study
examining erythrocyte CA level in hepatic cancer.
HCO
Trace elements are required for many metabolic and
physiological events in the body. Therefore, the imbal-
ance of trace element levels will adversely influence bio-
logical processes in vivo, resulting in the occurrence of
various diseases. Epidemiological studies demonstrated
that trace elements play a role in the etiology of many
diseases, including cancer [14].
It was determined that some trace elements are related
to the occurrence of HCC. For example, it was found that
the incidence of HCC was 10 times higher in subjects
with excess iron (without primary hemochromatosis) in
comparison with normal subjects [15]. Although it is not
clearly specified how Fe contributes to the occurrence
and growth of cancer, the possible mechanism is that Fe
leads to secondary damage in nucleic acids by promoting
production of free oxygen radicals [16]. Similarly, cop-
per is a predisposing factor in the occurrence of HCC,
since it plays role in hepatic damage [17]. In combination
with Fe, Cu leads to production of free oxygen radicals,
which damage cellular organelles. If copper levels in-
creases (similar to iron), the production of highly reactive
oxygen species increases, which lead to peroxidation of
membrane lipids, direct oxidation of proteins and dam-
age of DNA and RNA molecules [18]. In contrast, Zn
alleviates pro-oxidative toxic effects, which are secon-
dary to excess or insufficient intake of some substances,
and thus, it produces a hepatoprotective effect [19]. A
higher in vivo level of carcinogenic metals, such as lead
and cadmium, may result in some physiological disorders.
For example, cadmium is a strong carcinogenic sub-
stance in humans and it was found that environmental
exposure leads to cancer of the prostate, kidneys and
pancreas, and in particular, the lungs [20]. Similarly, it
was suggested that environmental exposure to lead is re-
lated to the occurrence of esophageal, hepatic and blad-
der cancers [21].
The current study was conducted to the determine se-
rum levels of trace elements and heavy metals and to
quantify the activity levels of erythrocyte catalase and
carbonic anhydrase enzymes in patients with primary and
metastatic hepatic cancer.
2. Material and Method
A total of 40 patients with hepatic cancer were enrolled
in the current study and 29 healthy controls. In the study,
blood samples were drawn from patients who were ad-
mitted to the Oncology Clinic of Training and Research
Hospital, Medical Faculty, Yüzüncü Yıl University and
were diagnosed with cancer in the light of radiological
and histopathological examinations, and from healthy
subjects. Cancer patients and control subjects were simi-
lar in terms of age and gender. The mean age of cancer
patients was 45 - 65 years, and in this group, eight sub-
jects were female and 32 subjects were male. Of the
healthy subjects forming the control group, six were fe-
male and 23 were male, while the mean age was 48 - 65
years. Considering histopathological tumors, it was de-
termined that 14 patients had primary hepatic cancer,
while 26 patients had metastatic hepatic cancer. Metasta-
sis from various organs (esophagus, stomach, colon and
small intestine) to the liver was determined in 26 subjects
in the cancer group. Patients who were newly diagnosed
and patients with a history of anti-cancer therapy were
excluded. In the current study, approval was obtained
from the Local Ethics Committee of Clinical and Labo-
ratory Studies, Training and Research Hospital, Medical
Faculty, Yüzüncü Yıl University, before blood samples
were drawn. In addition, written consent was obtained
from patients and healthy subjects before blood samples
were drawn.
Venous blood sample of 7 ml was drawn from each
study subject, including healthy controls and patients.
Serum was obtained by centrifuging the blood sample at
3500 rpm/min for 10 minutes and the plasma and buff
coat were removed. Samples were stored at −80˚C until
they were analyzed. Trace elements, minerals and heavy
metals (Pb, Cd, Mn, Cu, Mg, Zn, Fe and Co) were de-
termine in serum samples of all study subjects with Ato-
mic Absorption Spectrophotometer (AAS: UNICAM-
929 Spectrophotometer, Unicam Ltd., York Street, Cam-
bridge, UK). Erythrocyte samples were prepared to mea-
sure catalase and carbonic anhydrase enzyme activities.

Investigating Catalase and Carbonic Anhydrase Enzyme Activities and Levels of Certain Trace Elements
and Heavy Metals in Patients with Primary and Metastatic Hepatic Carcinoma 1375
Blood samples were added to EDTA (Ethylenedia-mine-
tetracetate) tubes to prepare erythrocyte specimen and
plasma was obtained by centrifuging samples at 3500
rpm for 10 minutes. Plasma was discarded and remaining
part was irrigated with saline (0.9% NaCl). Resultant up-
per phases were separated and discarded, and a pure ery-
throcyte pack was prepared by repeating this process
three times. Carbonic anhydrase and catalase enzyme
activities were analyzed in erythrocyte pack samples.
Carbonic anhydrase activity analysis was carried out
according to the method, which was developed by Maren
and colleagues [22]. This method is based on the princi-
ple of measuring time, which elapses to decrease pH
from 10 to 7.4 due to H+ ion released secondary to hy-
dration of CO2. The indicator was phenol red since pH is
associated with color change at pH = 7.4.
Activities were determined as follows: First, 2 ml of
indicator (phenol red) and 1.5 ml of saturated CO2 solu-
tion were added into reaction tube. CO2 gas was passed
from pure water at 0˚C for half an hour in order to pre-
pare a saturated CO2 solution). Enzyme solution (0.1 ml)
was added to this mixture. At the same time, 0.4 ml of
carbonate buffer was added to the solution and time was
measured, which elapsed for conversion of red to yellow,
and result was expressed as Tc. Pure water was added to
the blank solution tube (rather than 0.1 ml of enzyme
solution) and the same procedures were repeated to de-
termine To. In this method, for CA enzyme activity, one
enzyme unit (EU) is defined as amount of enzyme which
halves time of non-enzymatic CO2 hydration.
Using the formula


occ
EUtt t , enzyme unit
was analyzed in the volume of eluate used [22].
Catalase enzyme activity was measured according to
Aebi method [23]. H2O2 was disintegrated and removed
from the analysis environment and the resultant reduction
of absorbance was read at 240 nm. Activity was deter-
mined as follows. First, two tubes were made ready; 0.1
ml of enzyme (erythrocyte) was added to the first tube
and pure water was placed into the second tube instead of
erythrocyte and 2.8 ml of phosphate buffer was added to
both tubes. Next, 0.1 ml of H2O2 was added to both tubes
and they were vortexed. Activity was analyzed at 30-
second intervals for 3 minutes and next. The change in
absorbance was monitored at 240 nm using a spectro-
photometer (Shimadzu UV-1201, Japan).
Statistical Analysis: Parameters were expressed as
mean ± standard error (SE) and a P value <0.05 was con-
sidered statistically significant. Statistical analysis was
carried out according to student’s t test. Statistical ana-
lyses were carried out using the SPSS® statistical soft-
ware package (SPSS for Windows version 13.0, SPSS
Inc., Chicago, Illinois, USA).
3. Results
Descriptive features of study subjects are shown in Table
1. As it can be seen in the table, mean age of patients
with primary and metastatic hepatic carcinoma was close
to that of control subjects. Of subjects in the patient
group, 26 had metastatic hepatic cancer, while 14 had
primary hepatic cancer.
Carbonic anhydrase (CA) and catalase (CAT) enzyme
levels and relevant statistical analyses of control subjects
and patients with primary and metastatic hepatic cancer
are shown in Table 2. As it can be seen in Table 2, car-
bonic anhydrase values were higher in patients with pri-
mary and metastatic hepatic cancer in comparison with
that of control subjects. In addition, in the group of me-
tastatic hepatic cancer, serum CA level was significantly
higher than that of primary hepatic cancer group. More-
over, in comparison with the control group, catalase
(CAT) level was low in the primary and metastatic he-
patic cancer groups. There was no significant difference
between the primary hepatic cancer group and the me-
tastatic hepatic cancer group with respect to CAT level
(P > 0.05).
Trace element and heavy metal levels and relevant sta-
tistical analyses of control subjects and patients with
primary and metastatic hepatic cancer are shown in Ta-
ble 3. It was observed that in comparison with the control
group, serum iron (Fe), cobalt (Co), cadmium (Cd) and
Table 1. Descriptive features of control subject and patients
with liver cancer.
Number of
male subject
Number of
female subject Mean age
Primary hepatic
cancer 10 4 45 - 65
Metastatic
hepatic cancer 19 7 45 - 65
Control group 23 6 48 - 65
Table 2. Catalase and carbonic anhydrase enzyme activity
levels in primary and metastatic hepatic cancer patients
and control subjects.
Primary
(n = 14)
Metastatic
(n = 26)
Control
(n = 29)
CA (EU/gHb) 0.452 ±
0.0368 a*
1.161 ±
0.0401 A
0.111 ±
0.00806
CAT (EU/gHb)16.094 ±
1.774 b
13.599 ±
0.516 B
61.480 ±
0.210
#Values are expressed as mean and (±) standard error. *It implies the statis-
tical significance between primary and metastatic hepatic cancer patients (P
< 0.0005). (a, b) Statistical significance between primary hepatic cancer
patients and control subjects (P < 0.005). (A, B) Statistical significance
etween metastatic hepatic cancer patients and control subjects (P < 0.005). b

Investigating Catalase and Carbonic Anhydrase Enzyme Activities and Levels of Certain Trace Elements
and Heavy Metals in Patients with Primary and Metastatic Hepatic Carcinoma
1376
Table 3. Some mineral, trace element and heavy metal levels in primary and metastatic hepatic cancer patients and control
subjects.
Primary (n = 14) Metastatic (n = 26) Control (n = 29)
Fe (μg/dI) 0.917 ± 0.182 c 0.49 ± 0.0311 C 0.0871 ± 0.009
Mg (μg/dI) 11.711 ± 0.567 d* 6.044 ± 0.114 D 23.877 ± 0.418
Mn (μg/dI) 0.047 ± 0.003 e 0.0642 ± 0.00454 E 0.253 ± 0.012
Zn (μg/dI) 0.917 ± 0.083 f* 0.0455 ± 0.0102 F 2.243 ± 0.0339
Cu (μg/dI) 0.953 ± 0.068 g* 2.348 ± 0.032 G 3.231 ± 0.0487
Co (μg/dI) 0.024 ± 0.004 h* 0.211 ± 0.0112 H 0.00571 ± 0.000317
Cd (μg/dI) 0.004 ± 0.00072 k* 0.0619 ± 0.00496 K 0.00056 ± 0.00004
Pb (μg/dI) 0.273 ± 0.035 m* 0.937 ± 0.020 M 0.0587 ± 0.018
#Values are expressed as mean and (±) standard error. *It implies the statistical significance between primary and metastatic hepatic cancer patients (P < 0.0005).
(c, d, e, f, h, k, m) It implies the statistical significance between primary hepatic cancer patients and the control subjects (P < 0.005). (C, D, E, F, G, H, K, M) It
implies the statistical significance between metastatic hepatic cancer patients and the control subjects (P < 0.005).
lead (Pb) levels were high in primary and metastatic he-
patic cancer groups, while serum magnesium (Mg), man-
ganese (Mn), Zinc (Zn) and Copper (Cu) levels were low
(P < 0.05) (Table 3).
4. Discussion
The current study was conducted to determine cytosolic
erythrocyte carbonic anhydrase and catalase enzyme ac-
tivities and levels of some trace elements and heavy met-
als.
Free radicals can be produced due to many reasons,
including ultraviolet rays, metal-catalyzed reactions and
atmospheric pollution [24]. It is known that free radicals
have effects on occurrence and growth of cancer [25].
Anti-oxidant substance, including catalase, eliminates
free radicals, resulting with alleviation of cellular dam-
age and in conclusion, it may prevent or delay occur-
rence of cancer, aging and chronic diseases. [25,26]. Bel-
lisola et al. (1987) found that catalase enzyme activity
was low in tumor tissue of patients with HCC and in the
light of this finding, they suggested that the anti-oxidant
system was impaired in liver cancer [27]. In another
study investigating CAT levels in a total of 125 patients
with lung, lymphoma, breast and head and neck cancers,
it was found that the CAT level was lower in all types of
cancers, particularly in lymphoma, in comparison with
the control group [28]. Lin and Yin (2007) examined
CAT and SOD (superoxide dismutase) levels in 40 pa-
tients (age range: 37 - 80 years) who had recently diag-
nosed hepatocellular carcinoma and had no history of
previous medical treatment, and they found that CAT and
SOD activity levels were significantly low in the patient
group [29]. Similar to those studies, our study also de-
termined that catalase enzyme activity significantly de-
creased in both primary hepatic cancer and metastatic
hepatic cancer groups. In contrast, there was no statisti-
cally significant difference between the primary hepatic
cancer group and the metastatic hepatic cancer group (P
> 0.05; Table 2). Erythrocyte catalase activity can possi-
bly be an indicator of oxidative stress. The balance be-
tween pro-oxidant and anti-oxidant substances impairs in
cancer patients, resulting in oxidative stress and cellular
damage. Low erythrocyte catalase activity in hepatic
cancer may be an indicator of deficiency in the anti-oxi-
dant system of cancer patients.
Some studies had determined that carbonic anhydrases
played a significant role in malignant cerebral tumors
and gastric and pancreatic cancers [11]. The enzymes of
the carbonic anhydrase family play an important role in
extracellular acidification, and several studies have sug-
gested that the acidic environment facilitates and pro-
motes tumor growth [30]. A study examined cytosolic
erythrocyte CA (I, II) levels in various types of cancers
(stomach, prostate, lung, ovary), and it was found that the
CA level was higher in the cancer group in comparison
with the control group [31]. In another study examining
CA levels in hematologic diseases, particularly leukemia,
it was noted that in comparison with the control group,
CA (I, II) levels were higher in the patient group [30]. In
the current study, CA values were higher in patients with
primary and metastatic hepatic cancer in comparison
with the control subjects. The difference was statistically
significant (P > 0.05). In addition, in the group of metas-
tatic hepatic cancer, the serum CA level was higher than
that of primary hepatic cancer group (P < 0.05; Table 2).
We did not have the opportunity to make comparisons
since we could not find another study examining eryth-
rocyte CA level in liver cancer. However, higher cytoso-
lic erythrocyte CA level in patients with liver cancer is

Investigating Catalase and Carbonic Anhydrase Enzyme Activities and Levels of Certain Trace Elements
and Heavy Metals in Patients with Primary and Metastatic Hepatic Carcinoma 1377
suggestive of the possibility that this enzyme may play a
significant role in pathophysiology and diagnosis of liver
cancer. However, larger studies are required in order to
completely understand how the enzyme level will change
depending on type of cancer or stage.
Magnesium (Mg) is a macro-element with anti-oxidant
effects, which participates to more than 300 anti-oxida-
tive enzymatic reactions [32]. In association with oxida-
tive stress, magnesium deficiency plays a role in aging
and the occurrence of geriatric diseases. Although the
relation cannot be clearly evidenced in human, it was
shown that Mg deficiency promotes oxidative stress in
experimental animals [33]. In a study examining many
macro-elements and trace elements, cancer patients were
compared with healthy subjects and it was found that the
serum Mg level was lower in the cancer group. Low se-
rum Mg level can be secondary to the fact that the ele-
ment is consumed in some metabolic pathways or re-
placed with carcinogenic metals in the occurrence and
growth of cancer [34]. In the current study, similar to
findings written above, serum Mg levels were signifi-
cantly lower in patients with primary and metastatic he-
patic cancer in comparison with the control subjects (P <
0.05). In addition, in the group of metastatic hepatic
cancer, serum Mg level was lower than that of the pri-
mary hepatic cancer group (Table 3).
Copper (Cu) plays a role in the production of free oxy-
gen radicals, which damage cellular organelles [35] Thus,
excess Cu leads to hepatic damage and facilitates the
occurrence of cancer. Several studies found that in HCC
patients Cu level was higher in tumor tissue in compari-
son with the surrounding tissue [36]. In contrast, some
studies reported that Cu level was lower in the tumor
tissue of patients with metastatic liver cancer in com-
parison with normal hepatic tissue [37]. In the current
study, the serum Cu level was lower in patients with
primary and metastatic hepatic cancer in comparison
with the control subjects (P < 0.05). In addition, in the
group of primary hepatic cancer, the serum Cu level was
lower than that of the metastatic group (P < 0.05; Table
3).
Manganese (Mn) plays an important role as cofactor of
many enzymes [38]. Manganese is a trace element,
which is necessary for the activity of SOD enzyme, an
important member of the anti-oxidant system [39]. In the
current study, the serum Mn level was lower in patients
with primary and metastatic hepatic cancer in compari-
son with healthy subjects (P < 0.05). In addition, in the
primary group, Mn level was lower than that of the me-
tastatic group, but the different was not statistically sig-
nificant (P > 0.05; Table 3). Low Mn level may impair
the balance between oxidant and anti-oxidant substances
and it may also weaken the anti-oxidant system. In a
study evaluating serum trace element levels and total
anti-oxidant status in patients with breast cancer, authors
found that the Mn level was significantly lower in the
patient group in comparison with the control group [40].
Takikawa (1990) determined that serum Mn levels did
not vary between patients with HCC and control subjects
[41].
Iron (Fe) plays a role in the transportation of oxygen,
ATP production and DNA synthesis. In addition, it is
included in the prosthetic group of the catalase enzyme
[42]. Free forms of Fe may exert toxic effects in viable
cells. The toxicity may lead to the production of active
oxygen species, resulting in the promotion of lipid per-
oxidation and attacks on DNA molecules [43]. In the
current study, the serum Fe level was significantly higher
in patients with primary and metastatic hepatic cancer in
comparison with the control group (P < 0.05). In contrast,
there was no statistically significant difference between
the primary hepatic cancer group and metastatic hepatic
cancer group (P > 0.05; Ta ble 3). It can be speculated
that high Fe level is an important factor in the occurrence
of liver cancer, since it may result in oxidative damage.
Another study found that the Fe level was lower in the
tumor tissue of patients with primary liver cancer in
comparison with normal surrounding tissue [44]. Feng et
al. (2012) conducted a study on patients with breast can-
cer and similar to the findings of the current study, they
determined that the serum Fe level was higher in com-
parison with the control group. In the light of this finding,
they suggested the view that a high serum Fe level can be
a risk factor for breast cancer [40].
Zinc (Zn) protects sulfhydryl groups of proteins
against attacks of free radicals and it decreases the pro-
duction of free radicals by inhibiting redox-active transi-
tion metals (Fe, Cu) [45]. A study was conducted to
evaluate levels of trace elements in tumor tissue of pa-
tients with metastatic liver cancer and it was found that
Zn level was lower in tumoral tissue in comparison with
the tissue surrounding the tumor and the control group
[37]. Some studies were performed in patients with HCC,
tumor tissue levels of Zn, were found to be lower than
the surrounding tissues [46]. In the current study, the
serum Zn level was lower in patients with primary and
metastatic hepatic cancer in comparison with healthy
subjects (P < 0.05). In addition, in the metastasis group,
the serum Zn level was lower than that of the primary
group (P < 0.05; Tabl e 3). Although it is thought that
levels of zinc are low in cancer due to oxidative stress or
cellular use of zinc and changes in secretion, the mecha-
nism could not be completely clarified [47].
In the occurrence or growth of cancer, the role of co-
balt (Co) compounds is not clearly clarified. Although
there is no definitive evidence indicating that Co com-
pounds lead to cancer in humans, animal studies proved
that cobalt powders (Cobalt oxide and Cobalt sulphide)

Investigating Catalase and Carbonic Anhydrase Enzyme Activities and Levels of Certain Trace Elements
and Heavy Metals in Patients with Primary and Metastatic Hepatic Carcinoma
1378
lead to the occurrence of cancer [48]. Pasha et al. (2008)
determined that there was no statistically significant dif-
ference between the group of cancer patients and the
control group with respect to Co level [34]. Another
study examined some trace elements and vitamins in 20
patients with prostate cancer and found that serum Co
level was higher in the group of cancer patients relative
to the control group [49]. In the current study, serum Co
level was higher in patients with primary and metastatic
hepatic cancer in comparison with the control group (P <
0.05). In addition, in the group of metastatic hepatic
cancer, serum Co level was higher than that of primary
hepatic cancer group. There was statistically significant
difference between groups (P < 0.05; Table 3). Further
studies are needed to better understand potential hazards
of cobalt on human whether leads to cancer.
Cadmium has been designated a human carcinogen by
the IARC (International Agency for Research on Cancer)
[50]. Cadmium exerts many effects, via multiple mecha-
nisms of action, on the development of cancer. Some of
these include oxidative stress, prevention of DNA repair
and inhibition of apoptosis [51]. Cadmium is taken in
foods, air and respiration in small amounts and it accu-
mulates in the body over time [52]. Primary deposition
sites are the liver and kidneys. In addition, the element
may accumulate in the pancreas, prostate and heart [53].
In the current study, serum Cd level was significantly
higher in patients with primary and metastatic hepatic
cancer in comparison with the control group (P < 0.05).
In addition, in the metastasis group, serum Cd level was
higher than that of the primary hepatic cancer group (P <
0.05; Table 3). Armstrong and Kazantzis (1985) found
that the frequency of kidney diseases increased in work-
ers who were exposed to cadmium, and the severity of
the disease was related to exposure time and dose, while
frequency of prostate cancer mildly increased (although
not statistically significant) in workers who were exposed
to cadmium at moderate or high level [54]. Another
study examined 112 female and male patients with can-
cer and found that serum Cd level was 1.6- to 7.4-folds
higher in cancer patients in comparison with that of the
control group. High level of toxic metals, such as Cd, in
cancer patients (in comparison with healthy subjects)
indicates that those metals accumulate in the body and
replace macroelements [34].
IARC classified lead (Pb) as Group 2A carcinogenic
substance [55]. It is known that exposure to lead results
in cell proliferation in the liver, but the relation of this
finding with hepatic tumors could not be proven [56]. A
cohort study was conducted in Sweden on lead smelter
workers, who have occupational exposure to lead, and
cancer rates were examined; it was determined that some
types of cancers, particularly lung cancer, were more
common in those workers [57]. A study enrolled 154
newly diagnosed patients with renal cancer and it was
concluded that the serum Pb level was higher in the pa-
tient group relative to the control group and a high serum
lead level was related to the onset of renal cancer [58].
Similar to that study, the serum Pb level was higher in
patients with primary and metastatic hepatic cancer in
comparison with healthy subjects in the current study (P
< 0.05). In addition, in the metastasis group, the serum
Pb level was higher than that of primary group (P <0.05;
Table 3). In the light of these results, it can be speculated
that environmental exposure of lead is a risk factor for
some types of cancers, including liver cancer.
5. Conclusion
In conclusion, levels of trace elements vary in many
types of cancers. Further studies are required to better
understand the reasons and underlying mechanisms.
Lower catalase activity in cancer patients raises a ques-
tion. Is it the lower catalase activity that leads to the oc-
currence of cancer or does the anti-oxidant defense sys-
tem become weaker in the process of the development of
cancer? Further studies with larger populations are re-
quired to answer this question. Carbonic anhydrase iso-
enzymes have come to be of interest, since some recent
studies found that some iso-enzymes of carbonic anhy-
drase were higher in some types of cancers. However,
available studies are extremely limited, and the relation
between cancer and carbonic anhydrase could not be
clearly clarified. Higher erythrocyte carbonic anhydrase
levels in patients with hepatic cancer suggest that the en-
zyme can be a useful indicator in the diagnosis of the
cancer and this indicator may direct treatment of cancer.
However, larger studies should be conducted on this is-
sue.
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