International Research Journal of Biotechnology (ISSN: 2141-5153) Vol. 2(5) pp.093-102, April, 2011
Available online http://www.interesjournals.org/IRJOB
Copyright © 2011 International Research Journals
Full Length Research Paper
Use of formaldehyde as a novel agent for cancer
therapy
Prabir Chakravarty
Tumor Immunity and Gene Therapy Unit, Chittaranjan Cancer Institute, S.P. Mukherjee Road, Calcutta-700 025, India.
Accepted 11 April 2011
Formaldehyde is a ubiquitous aldehyde found in the environment. However, its biological role has not
been fully understood. It is known to be extensively used in alternative forms of medicine for treating a
wide range of diseases including proliferating disease like cancer. However, there is no study on its
possible role in experimental cancer therapy. The present study was undertaken to explore the possible
role of formaldehyde in cancer and its implications, if any in cancer therapy. Experiments were carried
out in vitro and in vivo to investigate the probable role of formaldehyde in proliferation, cytotoxicity and
in cancer therapeutics. The study revealed that formaldehyde at a lower concentration of 50ng/ml
increased proliferation of tumor cells. However, when the concentration was enhanced, an inhibitory
effect on tumor cell proliferation was noted. A formaldehyde concentration of 200ng/ml was cytotoxic to
tumor cells in vitro. To ascertain its in vivo effectiveness for cancer therapeutics, tumor bearing
animals were administered with different concentrations of formaldehyde and monitored; the end point
being survival of the animals. It was demonstrated for the first time that formaldehyde at a
concentration of 118.4µ
µg/ Kg body weight had a therapeutic effect on tumor bearing animals. This
concentration was found to be cytotoxic to tumor cells in vivo without causing any adverse effect on
the physiology of animals, About 25% of treated tumor bearing animals survived for more than four
months following tumor cell transplantation compared to untreated tumor bearing animals, all of which
died within one month of tumor cell transplantation. In conclusion It appears that an appropriate
concentration of formaldehyde has a therapeutic role without being cytotoxic to animals. This insight
could open a new vista for treating cancer in future.
Keywords: Formaldehyde, Cancer, Therapy, Cytotoxicity assay, Proliferation assay and Tumor
INTRODUCTION
Formaldehyde is a ubiquitous colorless, flammable,
strong-smelling chemical that is used in building
materials and to produce many household products. In
addition, formaldehyde is commonly used as an
industrial fungicide, germicide, and disinfectant, and as a
preservative in mortuaries and medical laboratories
(NIOSH, 1967). It occurs naturally in the environment
and is produced in small quantities by most living
organisms as part of their normal metabolic processes. In
humans and experimental animals, formaldehyde is
*Corresponding author Email: prabir9p@yahoo.com
readily absorbed by all exposure routes. When inhaled, it
reacts rapidly at the site of contact and is quickly
metabolized in the respiratory tissue. Humans
experience sensory irritation (eye, nose etc); though no
systemic toxicity has been observed following repeated
exposure to formaldehyde in animals and humans
(NIOSH, 1976).
Formaldehyde has long been known to have
carcinogenic property with direct association with the
etiology of some forms of cancer (Nordman et al, 1985).
The possible relationship between formaldehyde
exposure and cancer has been studied extensively in
experimental animals and humans. There is clear
evidence of nasal squamous cell carcinoma (SCC) from
094 Int. Res. J. Biotechnol.
inhalation studies in the rat, but not in mouse and
hamster. Although several epidemiological studies of
occupational exposure to formaldehyde have indicated
an increased risk of nasopharyngeal cancers, the data
are not consistent. The postulated mode of action for
nasal tumors in rats is biologically plausible and
considered likely to be relevant to humans. Recent
studies have suggested a possible link between exposure
to formaldehyde and nasal cancer as was hypothesized
based on epidemiological studies (Broughton and
Thrasher, 1988). An NCI case-control study among
funeral industry workers that characterized exposure to
formaldehyde also found an association between
increasing formaldehyde exposure and mortality from
cancers of the hematopoietic and lymphatic systems,
particularly myeloid leukemia (Collins and Lineker, 2004;
Checkoway et al, 2010).
However, formaldehyde is also known to have various
advantageous effects and is widely used in different
biological fields. It is used directly or in formulations in a
number of industries including medicine-related
industries (such as forensic/hospital mortuaries and
pathology laboratories). It is known to have disinfective
properties and is extensively used in tissue culture and in
the synthesis of pharmaceutical drugs (Olsen and
Dosing, 1982). Its role as tissue preservatives is also well
documented (Grammer et al, 1990). It is important to
note that formaldehyde does not have any adverse
effects on normal physiology of an organism up to a
dosage of 80mg/kg body weight (Thrasher et al, 1989).
Formaldehyde is also known to have systemic effects
when taken in vivo. The systemic changes include varied
Immune changes with formaldehyde exposure. Studies
have revealed changes in cell-mediated immunity like
changes in basophiles and/or suppressor cells (Pross et
al, 1987; Thraser et al, 1988; Thraser et al, 1990). It
could also influence the immune response indirectly by
increasing nitric oxide production through activation of
the brain vanilloid receptor (Palazzo et al, 2002).
Thus formaldehyde appears to be a versatile molecule
whose potential beneficial effects have not yet been fully
exploited. Though its importance has long been
recognized in some forms of alternative medical
practices like homeopathic medicine and as tissue
preservatives, not much research or application have
been done in main stream medicine. In homeopathic
medicine, formaldehyde is extensively used in very low
concentrations to treat various pathological conditions
including proliferative disease like cancer in humans
(Boericke, 2002). However, no exhaustive studies have
been conducted as yet and experimental evidences are
lacking to establish its usefulness for cancer therapy in
humans. In this direction, we have reported earlier that
formaldehyde have antiproliferative activity and may
have some use in therapy of cancer (Chakravarty et al,
1995). We hypothesized that formaldehyde at certain
concentrations may be effective in treating proliferative
diseases like cancer in vivo. In this study, extensive in
vitro and in vivo experiments were carried out in an
animal tumor model in an effort to ascertain its role if
any, in cancer. Here we show for the first time that
formaldehyde has both proliferative and anti-proliferative
property at different concentrations and its antiproliferative activity could be successfully exploited to
treat cancer in an experimental tumor model.
MATERIALS AND METHOD
Tumor Model
Studies were carried out with transplanted Earlich’s
Ascites Carcinoma (EAC) in vivo and in vitro. The cells
were maintained in vivo in the swiss mice by serial
passage. The animals received 1x107 tumor cells by ip
injection in the abdomen. The tumor volume reached its
maximum by day 17 and thereafter maintained a
stagnant condition. The animals eventually died between
20-25 days following tumor transplantation.
In vitro studies
In vitro studies were carried out to determine the effect of
formaldehyde (Fisher, NJ) on tumor cells.
Proliferation assay
For proliferation assay, the EAC cells were extracted,
washed and suspended in RPMI 1640 media containing
5
10% FCS. 100µl containing 1x10 cells were seeded in
each well of a 96 well plate. To each well freshly
prepared
formaldehyde
solution
at
different
concentrations were added for a final volume of 200
µl/well. For each concentration six wells were used.
Appropriate controls were used against the formaldehyde
treated cells. After 48 hours of incubation oneµci/µl of 3H
thymidine was added to each well and the incorporation
of 3H Thymidine by the EAC cells was determined in a
scintillation counter.
Cytotoxicity assay
For determining the cytotoxicity of formaldehyde on
tumor cells, 1x106 cells were seeded in each well of a 24
well plate. The concentration used for the cytotoxicity
assay was similar to that used in the in vivo study.
Hundred micro liters (µl) of formaldehyde solution (8
Chakravarty 095
µg/ml) was added in a final volume of 0.5 ml. After 48
hours, viability of the cells was checked by trypan blue
exclusion test. The results are expressed as percent •
dead cells. At least 500 cells were counted for the •
purpose
•
In vivo studies
Mice
Six to 8 week-old male (swiss strain) mice was obtained
from the Institutes animal Resources facilities and
maintained under controlled temperature, humidity, and
a 12h light: dark cycle with food and water ad libitum.
solution (a dose of 8µg/ml [118.4µg/ Kg body weight] in
the following schedule:
Group CI – For 10 consecutive days
Group CII – For 15 consecutive days
Group CIII – For 20 days; of which first 15 were
administered on consecutive days and the remaining five
were given at an interval of 2 days (a total of 25 days).
A group of 15 animals served as controls which received
0.4ml of normal saline for 20 consecutive days.
In order to determine the effect of the therapeutic dose
on normal mice, 15 normal animals were injected with
formaldehyde solution (118µg/kg body weight) for 20
consecutive days (Group E). The Group E animals were
regularly weighed and blood picture (total RBC count,
total WBC count, differential count was monitored
weekly. All the treated and non-treated tumor animals
were monitored for tumor growth.
Survival Studies
Statistics
Animals: Male, six to eight weeks old mice were used for
the study. The tumor strain used was EAC maintained in
ascetic form in the peritoneal cavity of the animals.
About 300 hundred animals were used for the entire
study.
For experimentation, each animal was injected ip with
viable 1x105 EAC cells in the peritoneal cavity. The
viability of the tumor cells was determined by counting
the tumor cells in an improved neubeur chamber by the
trypan blue exclusion test.
For establishing the effective therapeutic regimen of
formaldehyde based on the information of in vitro
studies, the animals were divided into four groups (group
A, B, C and D). For each group 30 animals were used.
Each animal from the respective groups and controls
5
were injected ip with viable 1x10 EAC cells in the
peritoneal cavity. Twenty four hours later each of the
animals from respective groups received the following
concentration of formaldehyde solution ip in a final
volume 0.4 ml:
• Group A : 2µg/ml [29.6µg/Kg body weight ]
• Group B ; 4µg/ml [59.2µg/ Kg body weight]
• Group C: 8µg/ml [118.4µg/ Kg body weight]
• Group D: 16µg/ml [236.8µg/Kg body weight]
All the animals belonging to different groups were treated
for 7 consecutive days with formaldehyde solution. The
animals were monitored for 4 months and beyond to
assess the therapeutic effect using survival as the end
point.
As the group C treated animals receiving a dose of
8µg/ml [118.4µg/ Kg body weight] showed increased
survival following treatment with formaldehyde. Further
modifications of the treatment regimen were deployed in
an effort to increase the efficacy of the treatment. In this
protocol, tumor bearing animals received formaldehyde
The statistical analysis was done by Student’s t-test. The
results were considered significant when p < 0.05.
The work was done at Tumor Immunity and
GeneTherapy Unit, Chittaranjan National Cancer
Institute, Calcutta- 700025, India. The animal use
protocol (AUP) was duly approved by the Animal ethics
committee of the Institute.
RESULTS
Incorporation of 3H-Thymidine by tumor cells in
presence of formaldehyde solution showed
increased proliferation
The result obtained in the proliferation assay is shown in
figure 1. The figure 1 shows that there was an inverse
correlation between tumor cell proliferation and
formaldehyde concentration. While no proliferation of
tumor cells was noted at a concentration of 200 ng/ml
and at a concentration of 100 ng/ml, there was however,
an increased proliferation in tumor cells, as reflected by
3
H-Thymidine incorporation, at a much lower
concentration of 50 ng/ml. The increase was 17% more
than that of the controls, suggesting an increased rate of
proliferation of tumor cells in presence of formaldehyde.
From this experiment, it was also ascertained that a
concentration of 200ng/ml could be suitable for inhibiting
tumor growth in vivo.
Formaldehyde is cytotoxic to tumor cells
The result obtained from in vitro cytotoxicity assay is
depicted in figure 2. It is evident from the figure that the
096 Int. Res. J. Biotechnol.
Figure 1. Effect of formaldehyde on tumor cell proliferation
The figure shows Incorporation of 3H-Thymidine by tumor cells in presence of formaldehyde solution.
An increased proliferation was noted at lower concentration while inhibition at higher concentration.
Figure 2. Effect of formaldehyde on tumor cell viability
The figure shows the viability of tumor cells in presence of formaldehyde. The figure shows that
formaldehyde was cytotoxic to tumor cells. The results are shown as mean ± SEM. The level of
significance when p< 0.05
cells treated with formaldehyde showed cytotoxicity at 48
hours of treatment. The percent of killed cells was as
high as 60% compared to controls. These tumor cells
also exhibited necrotic features with ruptured membrane
Chakravarty 097
Figure 3. survival of mice in different experimental groups treated with formaldehyde
The figure shows the survival of animals following treatment with formaldehyde at different
concentrations: Group A : 29.6µg/Kg body weight; Group B ; 59.2µg/ Kg body weight; Group C:
118.4µg/ Kg body weight, Group D: 236.8µg/Kg body weight, respectively. The level of significance
when p< 0.05.
while viewed under microscope.
Survival study
Increased survival of animals following treatment
with formaldehyde
The figure 3 shows the survival of mice in different
experimental groups treated with different concentration
of formaldehyde. It is evident from the figure that group
C mice injected with formaldehyde at a concentration of
118.4µg/ Kg body weight survived the maximum period
of time following tumor cell transplantation without
showing any signs of toxicity. However, with increase in
6
the number of tumor cells (1x10 ) there was no effect on
survival and the animals died by three weeks of tumor
cell transplantation as was the case of control animals
injected with similar number of EAC cells. This confirms
that tumor burden along with concentration of
formaldehyde is an important criteria for tumor control in
vivo. It is also to be noted that the animals in group A
and group B receiving lower concentration of
formaldehyde did not impact on survival rather they died
in similar time span or earlier like the untreated animals.
However, the animals receiving higher concentration of
formaldehyde (group D) did not impact on survival rather
they died in similar time span or earlier like the untreated
animals. This may be due to other responses generated
by formaldehyde administration. The study therefore,
showed that the used concentration of 8µg/ml or
118µg/kg body weight (Group C) was suitable for
therapeutic use when the initial cell number injected was
100,000. To increase the efficacy of the treatment
schedule on survival of tumor bearing animals, the dose
of 8µg/ml or 118µg/kg body weight was then tried in
different time schedule. The figure 4 shows the result
obtained from the study. It is evident from the figure 4
that the tumor bearing animals that did not receive any
treatment died by four weeks of tumor cell
transplantation. The treated animals however, showed
variable results. Some of the animals of group CI
survived for more than 12 weeks after tumor cell
transplantation. The earliest death due to tumor burden
was not before fifth week of tumor cell transplantation.
The other two groups (CII & CIII) had interesting results.
While they both showed death due to tumor burden from
eight weeks on wards; the rate slowed down gradually in
group CIII mice and about 25 percent of the animals
were surviving after 17 weeks of tumor cell
transplantation. In group CIII, however five animals died
without tumor burden at different time intervals following
098 Int. Res. J. Biotechnol.
Figure 4. survival of animals following formaldehyde treatment with improved schedule (Group C)
The figure shows the survival of animals following treatment with formaldehyde at the concentration of
118.4µg/ Kg body weight (Group C) with improved schedule as mentioned in methods section. The level of
significance when p< 0.05.
tumor transplantation. Two of them died during the 4th
week, one during the 8th week, one during 12th week and
th
one during the 13 week of tumor cell transplantation
respectively. The animals did not show any apparent
toxicity due to formaldehyde. The animals may have
died due to other causes. Studies have established
decisively that formaldehyde does not have any adverse
effect on normal physiology of an organism up to a
dosage of 80 mg/kg body weight (Grammer et al, 1990).
Animals following formaldehyde administration did
not show any toxic effect
The normal animals did not have any toxicity related to
formaldehyde at the dose that was used for therapy. The
table 1 shows that the hematological profile of animals
injected with normal saline and those injected with
formaldehyde solution at a dose of 8µg/ml or 118µg/kg
body weight (Group C) were in the similar range. Earlier
studies have also established that formaldehyde does not
have any adverse effects on normal physiology of an
organism up to a dosage of 80 mg/kg body weight
(7Grammer et al 1990). However, contrarily it was
observed, with time, the animals injected with
formaldehyde were less susceptible to infection when
compared to controls suggesting a possible improved
immune response of the animals bearing the tumor.
DISCUSSION
This study reveals for the first time the in vivo anti-cancer
property of formaldehyde. Here it is reported that
formaldehyde used at a concentration of 8µg/ml or
118µg/kg body weight is very effective in inhibiting tumor
cell proliferation and increasing survival without being
toxic to animals bearing a poorly immunogenic
transplantable tumor.
Formaldehyde is a colorless chemical that occurs
naturally in the atmosphere through a variety of
biological and chemical processes. It is also physically
present in the human body at very low concentrations as
a result of various metabolic processes. It is water
soluble and biodegradable and is known to be associated
with minor uneasiness like headache, eye and respiratory
irritation, sleep disturbance and increased thirst at
exposure levels as low as 0.13 ppm (Thraser et al, 1990].
Chronic exposure to formaldehyde could cause
asthmatic symptoms and other reactive airway disease,
chronic fatigue, and increased sensitivity to chemicals
(Thraser et al, 1990). However, recent studies suggest
Chakravarty 099
Table 1: Blood profile of animals following formaldehyde administration
The table shows the blood profile of animals following formaldehyde administration. The administration of
formaldehyde did not show any toxic effect on the animals. The results are shown as Results are expressed as mean
±SEM. The level of significance when p< 0.05.
that there is no adverse effect of formaldehyde on
normal physiology of an organism up to a dosage of 80
mg/kg body weight (Grammer et al 1990). Our in vivo
studies were based on a formaldehyde concentration of
118µg/kg body weight, which is minimal compared to the
suggested dose in literature (Grammer et al, 1990).
We have shown that addition of formaldehyde
stimulated proliferation of tumor cells in vitro. Recent in
vitro studies have also corroborated with the fact that
formaldehyde may help in cell proliferation at a minimal
concentration of 25µM (Tyhiak et al, 2001; Szende and
Tyhiak 2010). In another study, enhanced cell
proliferation and reduced apoptotic activity at
concentrations of 0.5 and 0.1 mM of formaldehyde was
noted (16 Szende and Tyhiak 2010). Our present in vitro
study showed that tumor cells behave differently when
exposed at diverse range of formaldehyde concentration.
At a concentration of 50 ng/ml a significant proliferation
of tumor cells was noted compared to control tumor cells,
while no proliferation of tumor cells were noted at a
higher concentrations of 200 ng/ml and 100 ng/ml,
respectively. At this concentration tumor cells were
stimulated to grow at a more rapid rate (17%) compared
to non-exposed cells suggesting the possibility of a
‘promoter’ role of formaldehyde on tumor cell
proliferation. Thus it is plausible to assume that
continuous exposure to formaldehyde for cancer patients
may be harmful. This led us to further hypothesize that
formaldehyde may act as a ‘promoter’ to already
transformed cells which could result in acceleration of
tumor burden on continuous exposure. However, at a
higher formaldehyde concentration of 200 ng/ml an
opposite effect was noted. At this dose formaldehyde
was cytotoxic to tumor cells and there was no
incorporation of tritiated thymidine at this concentration.
Thus the study showed that at a higher concentration it
could be suitable for inhibiting tumor growth in vivo. This
observation was also supported by the results obtained in
the in vtro cytotoxicity assay wherein more than 60% of
tumor cell died in presence of formaldehyde by 48 hours
of formaldehyde exposure. These cells appeared to be
necrotic following exposure to formaldehyde. Similar cellnecrosis in presence of formaldehyde has been noted
recently by others (Saito et al 2005; Szende and Tyhiak,
100 Int. Res. J. Biotechnol.
2010). Tumor cell and endothelial cell culture studies
showed that formaldehyde at a concentration of 10 mM
caused necrotic cell death (Szende and Tyhiak, 2010)
and that formaldehyde and reactive oxygen species
(ROS), such as free radicals, are cytotoxic to the cells
(Saito et al 2005). Studies with U2OS cells showed that a
50% inhibition of cell growth was noted at 3mM
concentration of formaldehyde and this inhibitory effect
was influenced by intracellular GSH levels. A higher
GSH level protected cells against formaldehyde induced
cytotoxicity. It was observed that addition of a GSH
precursor, 2-oxothiazolidine-4-carboxylic acid (OTZ), had
a protective effect on formaldehyde-induced cytotoxicity
(Ho et al, 2007]. The free radicals induced GSH
reduction, whereas the formaldehyde resulted in the
formation of DNA-protein cross-links, with, increase of
cellular ROS and cell death was brought about by this
combination (Saito et al, 2003). However, It may be
interesting to point out that in plants endogenous
formaldehyde apparently plays a major role in regulation
of
normal
apoptosis
and
cell
proliferation.
These studies including ours clearly establish that
formaldehyde has a potential role in regulating cell
proliferation and cell death in biological system.
Unfortunately, given its apparently adverse chemical
nature and lack of knowledge on its biology, no serious
studies has been undertaken on its possible use in
biological therapy of different pathologies including
cancer. Here we have attempted to explore its biological
utility and the present data for the first time establishes
therapeutic efficacy of formaldehyde in cancer treatment.
Our in vivo study clearly demonstrated that formaldehyde
at a concentration of 118µg/kg body weight was effective
in controlling tumor growth and increasing survival of
tumor bearing animals without being toxic to the animals.
However, it is to be noted that with increase in the
number of tumor cells (x106) in vivo, formaldehyde
administration at the tested concentration failed to curb
tumor burden. The EAC cells used in this study is not
only highly tumorigenic but are poorly immunogenic so
further manipulation of the dose could yield better
results.
Toxicity of formaldehyde becomes a concern for its in
vivo application for any therapeutic usage. Earlier studies
have shown that administration of formaldehyde at a
dose of 80mg/kg body weight did not have adverse effect
on body weight, thymus, kidney, liver and cellularity of
spleen and lymph nodes. (Grammer et al, 1990). No
adverse effect of formaldehyde was noted on normal
animals in vivo. Our study clearly demonstrated that
formaldehyde did not have any unfavorable effect on the
general condition of the animals. On the contrary we
observed that formaldehyde seemed to improve the
general condition and immune status of the treated
animals as the tumor bearing animals were less prone to
infection. It is therefore reasonable to postulate that use
of formaldehyde at the suggested concentration may be
helpful in improving the health condition of advanced
cancer patients which could in turn improve their quality
of life that is nevertheless very important for cancer
patients. Some recent data have also pointed out the
possible therapeutic use of some chemicals like
methylated lysine residues and methylated arginine
residues in cancer (Szende and Tyhiak, 2010). In our
study, formaldehyde treated tumor bearing animals in
one group survived for more than 17 weeks after tumor
cell transplantation with out showing any signs of toxicity
to the chemical. Earlier studies have also established
that formaldehyde does not have any toxicity up to a
dosage of 80 mg/kg body weight (Grammer et al, 1990].
The toxicity of formaldehyde on cells may be related to
its ability to form adducts with DNA and proteins at
cytotoxic concentrations which is many folds more than
used in our experiments. At higher formaldehyde
concentrations, lipid peroxidation also takes place
resulting in cell death. (Yoshida et al, 2001). However,
there can also be a direct systemic response following
formaldehyde administration. Among immune changes
reported with formaldehyde exposure, include changes in
cell-mediated immunity involving changes in basophiles
and/or suppressor cells (NIOSH, 1967). Chronically ill
persons after formaldehyde exposure often exhibit
immune activation and increased autoantibody formation
(NIOSH, 1967; Olsen and Dosing 1982). Formaldehyde
also has the ability to stimulate the brain vanilloid
receptor that in turn could increase the release of various
immune substances (Broughton and Thrasher, 1988).
The killing of cells in vivo may be as a result of direct
action of formaldehyde or through systemic response.
Some studies have shown that cell death resulting from
formaldehyde action is necrotic rather than apoptotic
(Saito et al 2005). We also have observed that the cells
show necrotic features following 48 hours of
formaldehyde treatment. Additionally the dead and dying
cells could help in generating cytotoxic T Cells (CTL)
against the tumor. The apoptotic and necrotic cells are
immunogenic and are known to be taken up by dendritic
cells (DCs) that stimulate cytotoxic T Cells (CTL) to
produce a specific immune response against a tumor
(Albert et al, 1998a, Albert et al 1998b). DCs have been
shown to efficiently phagocytose dead cells and elicit
antigen-specific immune responses (Albert et al 1998a;
Albert et al, 1998b, Shaifmuthana et al 2000). It was
also demonstrated that Immunization with DCs pulsed
with apoptotic tumor cells could prime tumor specific
CTLs and confer protection against a tumor challenge in
a mouse model (Ronchetti et al, 1999). We also have
reported earlier that local irradiation of a tumor followed
by cytokine therapy can induce immune response in a
metastatic murine lung cancer model (Chakravarty et al,
1997). And using a prostate cancer model, we
Chakravarty 101
demonstrated that DCs are activated in presence of dead
and dying tumor cells (Chakravarty et al, 2007). Thus,
the antigens from dead and dying tumor cells can be
processed and presented in context of MHC class I by
DC that stimulates CD8+ T cells effectively in vitro and in
vivo (Sauter and Albert, 2000, Joke et al 2000). Further
the dead and dying cells also are effective in
immunization protocol (Chakravarty et al, 2006).
Formalin-fixed autologous melanoma cells have a
potential to function as effective antigen sources for
immunotherapy (Obataa et al, 2004]. Similar events may
be taking place in the present context wherein formalin
induced dead and dying tumor cells may be taken up by
DCs, which in turn could generate tumor specific T cells
that impacted on survival of animals. We have observed
in a different study that formaldehyde treated tumor cells
can generate tumor specific immune response
(Unpublished data). However, it was noted in a recent
study that formaldehyde causes immune suppression
only at a higher concentration of 150 ppm in fish
(Halladay et al, 2010). The study showed that exposure
to formaldehyde at higher concentrations decreased
peripheral blood lymphocytes, hematopoietic progenitors
and natural killer cell cytotoxicity (Halladay et al 2010). A
much lower concentration was used in the effective
group in our study.
Thus formaldehyde appears to be an enigmatic
molecule whose beneficial effect has not been fully
exploited. From our study it is established that
formaldehyde has a tumor stimulatory role in lower
concentration and at an appropriate dose it is therapeutic
to animals bearing tumor. Proper manipulation of this
molecule could open a new vista in the treatment of
cancer in near future.
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