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*Corresponding author: E-mail: pkorisadiran@pgschool.lautech.edu.ng; 
 
 
 

Asian Journal of Immunology 
 
2(1): 1-10, 2019; Article no.AJI.52086 
 

 
 
 

 

Assessment of Post Exposure of Benzene on Some 
Hematology Parameters and DNA Lesions on Adult 

Wistar Rats 
 

Orisadiran Patrick Kunle1*, Adedeji Adebayo Lawrence1,  
Adedeji Abiodun Oluwabusola2 and AbdulRahman AbdulFatai3 

 
1
Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. 

2Department of Anatomy, Olabisi Onabano University, Ago Iwoye, Nigeria.  
3
Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. 

 
Authors’ contributions  

 
This work was carried out in collaboration among all authors. Author OPK designed the study and 
wrote the first draft of the manuscript. Author AAO performed the statistical analysis. Author AAL 

wrote the protocol, author ARAF managed the analyses of the study. All authors read and approved 
the final manuscript. 

 
Article Information 

 
Editor(s): 

(1) Dr. Jaffu Othniel Chilongola, Department of Biochemistry and Molecular Biology, Kilimanjaro Christian Medical University 
College, Tumaini University, Tanzania. 

Reviewers: 
(1) Raquel Salazar-Lugo, Universidad de Oriente, Venezuela. 

(2) Byron Baron, University of Malta, Malta. 
Complete Peer review History: http://www.sdiarticle4.com/review-history/52086 

 
 
 
 

Received 08 August 2019  
Accepted 16 October 2019 

Published 22 October 2019 

 
 

ABSTRACT 
 

Aims: The study sought to investigate the effect of post-exposure of benzene on some 
haematology parameters and DNA lesions on adult wistar rats.   
 Methods: A total of twenty-eight rats were grouped into 4 groups, with group 1 serving as a 
control. The remaining 3 groups were interperitoneally administered 0.2 ml of benzene 48 hourly for 
4 weeks and were left of 0, 3 and 6 weeks respectively before sacrifice.  
Results: The result obtained showed that White Blood Cell (WBC), Red Blood Cell (RBC) and 
platelet counts were significantly reduced in benzene post exposed groups (p<0.05). 8-
hydroxydeoxyguanosine generation in liver and bone marrow were significantly higher in benzene 
post exposed groups. The photomicrograph of blood film of benzene exposed group showed 
promyelocyte and myeloblast. 

Original Research Article 



 
 
 
 

Orisadiran et al.; AJI, 2(1): 1-10, 2019; Article no.AJI.52086 
 
 

 
2 
 

Conclusion: It is concluded that benzene and its metabolite are highly toxic and are potentially 
damaging agents to the hematopoietic system. Evidence from our study suggested that elevated 
levels of 8-OHdG in liver and bone marrow compare to control would be a sign of increased 
oxidative stress, impaired antioxidant defence or inadequate repair of oxidative damaged DNA. 
 

 

Keywords: Interperitoneally; hematology; 8-hydroxydeoxyguanosine; promyelocyte; myeloblast; 
benzene. 

 

1. INTRODUCTION 
 

Benzene is an aromatic hydrocarbon and a 
component of crude oil and gasoline. It is a 
widely used chemical formed from both natural 
processes and human activities and a ubiquitous 
contaminant in the environment [1]. Occupational 
exposure to benzene occurs through solvent 
exposure in the chemical industry, in petroleum 
refineries, oil pipelines, on ships and tankers, bus 
garages and auto repair shops [2]. Human 
exposure to benzene occurs in diverse ways 
such as through dermal absorption, inhalation, 
ingestion of contaminated food and water, and 
active and passive tobacco smoking [3].   
 

Benzene exposure causes many adverse effects, 
such as skin irritation, inflammation of the nasal 
airways and throat, central nervous system 
depression, immunotoxicity and hematoxicity [4]. 
The cells of the hematopoietic system and bone 
marrow are the most sensitive target organs of 
benzene toxicity. Repeated occupational and 
non-occupational exposure to benzene over long 
periods may affect several hematopoietic 
parameters such as red blood cell, white blood 
cell and platelet counts [5] and eventually induce 
toxicity of the blood and blood forming organs. 
Benzene exposure is associated with increased 
risk of acute myeloid leukemia [6], multiple 
myeloma and non-Hodgkin’s lymphoma. Studies 
indicate that exposure to benzene produce 
toxicity and an increased risk of malignancies of 
the blood and blood-forming organs [7]. Benzene 
toxicity is linked to bone marrow depression, 
aplastic anemia, acute myeloblastic leukaemia 
and  acute non-lymphocytic leukemia [8]  and 
even  at low doses can  affect  white  blood  cell  
and  platelet counts [9]. This research was 
designed to study the immunotoxicity and 
hematotoxicity of post exposure to benzene in 
adult rats of Wistar strain. 
 

2. MATERIALS AND METHODS 
 

2.1 Chemicals and Reagents 
 
Citric acid, sodium citrate, sodium chloride and 
tris-hydrochloric acid were products of British 

Drug House (Pool, England). Benzene was 
obtained from Sigma, St. Louis MO while 8-
hydroxydeoxyguanosine assay kit was obtained 
from Cloud-Clone Corp, USA. The total protein 
kit was obtained from Fortress Diagnostics 
Limited (Muckamore, United Kingdom). All the 
chemicals and reagents were of analytical grade 
and were used and stored according to the 
manufacture’s instructions. 
 

2.2 Preparation of Reagents 
 
2.2.1 Citrate buffer  
 

21.01 g of citric acid and 29.41 g of sodium 
citrate were dissolved in 1 liter of distilled water 
each. 9.5 ml of citric acid solution was added to 
41.5 ml of sodium citrate solution and was made 
up to 100 ml and the pH was adjusted to 6.0 and 
stored at 4°C. 
 

2.2.2 Homogenizing buffers  
 

7.86 g of 50 mM Tris-HCl and 11.2 g of 
potassium chloride was dissolved in 900mls of 
distilled water and the pH was adjusted to 7.4. 
The solution was made up to 1 L and stored at 
4°C. 
 

2.3 Experimental Design 
 

A total of 28 Albino rats of Wistar strain, with an 
average weight of 190 g were obtained from the 
Animal house of Physiology Department, Ladoke 
Akintola University of Technology, Nigeria. The 
animals were divided into 4 groups and housed 
in separate cages in the same environment. The 
animals were allowed to acclimatize in the 
laboratory for two weeks before the 
commencement of the experiments. 
 

Benzene was administered to Wistar rats by 
interperitoneally injection of 0.2 ml of benzene 
solution, given every 48 hours for 4 weeks.   
 

The animals were randomly selected into 4 
groups, each containing 7 rats. 
 

Group I: Rats in this group served as the 
negative control. Group II: Rats in this group 



 
 
 
 

Orisadiran et al.; AJI, 2(1): 1-10, 2019; Article no.AJI.52086 
 
 

 
3 
 

were administered benzene for 4 weeks and 
were sacrificed immediately (0 week) after 
administration. Group III: Rats in this group were 
administered benzene for 4 weeks and were left 
for 3 weeks before sacrifice. Group IV: Rats in 
this group were administered benzene for 4 
weeks and were left for 6 weeks before sacrifice. 
 

2.4 Collection of Blood and Organs  
 

The rats were fasted overnight and sacrificed 
according to the experimental protocol. Blood 
was collected by cardiac puncture. Part of the 
blood was collected inside plain sample bottles 
(without anticoagulant), allowed to coagulate and 
then centrifuged at 3000 rpm for 15 minutes to 
obtain serum. The serum was kept under 
refrigeration at 4°C for biochemical parameters. 
The other part of the blood was collected into 
vacuum EDTA bottles, to be used for 
haematological parameters. 
 

2.5 Tissue Preparation 
 

The livers of the rats were excised, washed with 
normal saline solution and weighed. 1 g of the 
washed liver was homogenized in 5 ml 
homogenizing buffer (7.86 g of 50 mM Tris-HCl 
and 11.2 g of potassium chloride dissolve in 
900ml of distilled water, pH 7.4) using mortar and 
pestle. The homogenates were centrifuged at 
3000 rpm for 15 minto obtain the clear 
supernatant. The resulting homogenates were 
kept at 4ºC for biochemical parameters. 
 

2.6 Preparation of Bone Marrow Aspirate 
 
The femur and humorous bone of the sacrificed 
experimental mice were dissected and both the 
proximal and distal ends were removed by using 
the modified method of Saha, et al. [10]. Briefly, 
citrate buffer solution of pH 6.0 was injected 
gently into one end of the shaft. This process 
was followed to flush out the bone marrow 
through the opposite end into eppendoff tube to 
prepare and centrifuge at 3000 rpm for 15 
minutes to obtain the clear supernatant and 
pellet and were kept at 4°C for biochemical 
analysis. 
 

2.7 Determination of Haematological 
Parameters  

 

Haematological parameters were assessed by 
flow cytometry (direct current method) using 
suitable cell packs according to the 
manufacturer’s specification for the desired cell 
population on the SYMEX KX-21N autoanalyzer. 

2.8 Biochemical Examination 
 
The concentration of 8-hydroxyldeoxylguanosine 
(8-OHdG) in liver homogenate, bone marrow cell 
and bone marrow supernatant were measured 
using immunoenzymatic colorimetric method of 
DiaMetra, Italy (2008) and total protein 
concentration was determined in the serum and 
tissue homogenates by the Biuret (colorimetric) 
method [11] using FORTRESS Total Protein kit.  
 

2.9 Statistical Analysis 
 
Results are presented as Mean ± SD. Paired 
Student’s t-test was used to compare variations 
amongst groups. The minimum level of 
significance was considered at p˂0.05. Statistical 
analysis was carried out using a software 
program (GraphPad Prism Ver. 5; GraphPad 
Software, San Diego, CA). 
 

3. RESULTS 
 

3.1 Effects of Post Benzene Exposure on 
Haematological Parameters 

 

There was a significant decrease (P<0.05) in red 
blood cell counts of groups post exposed to 
benzene at week 0 (8.19 x 103 mm3), week 3 
(7.38 x 10

3
mm

3
) and week 6 (5.02 x 10

3 
mm

3 
; 

Figure 1) compared to the control (11.3 x 103 

mm3).  Similarly, there was a  significant (P<0.05) 
decrease in white blood cell counts of groups 
post exposed to benzene at week 0 (9.85 x 
10

9
/L), week 3 (4.46 x 10

9
/L)  and  week 6 (4.42 

x 103 mm3; Fig. 2) compared to the control (12.0 
x 10

9
/L). Platelet counts were significant (P<0.05) 

decrease in groups post exposed to benzene at 
week 0 (636 x 109/L), week 3 (563 x 109/L) and  
week 6 (510 x 10

9
/L) (Fig. 3) compared to the 

control (981 x 109/L)  
 

3.2 Effect of Post Benzene Exposure on 
8-Hydroxydeoxyguanosin (8-OHdG) 
Concentration  

 

There was a significant increase (P<0.05) in liver 
8-hydroxydeoxyguanosin concentration of group 
post exposed to benzene for 0 (0.61 ng/mg 
protein), 3 (0.59 ng/mg protein) and 6 (0.35 
ng/mg protein) weeks respectively (Fig. 4) 
compared to the control. Production of liver 8-
OHdG reduced during the post-exposure period; 
this it decreased between 4% and 43% from 
initial week to third week and third week to sixth 
week, respectively. There was also significant 
(P<0.05) increase in generation of 8-OHdG by 



 
 
 
 

Orisadiran et al.; AJI, 2(1): 1-10, 2019; Article no.AJI.52086 
 
 

 
4 
 

bone marrow cell in groups post exposed to 
benzene for 0 (0.29 ng/mg protein), 3 (0.46 
ng/mg protein) and 6 (0.71 ng/mg protein) weeks 
(Fig. 5) compared to the control (0.1651 ng/mg 
protein). The generation of 8-OHdG by bone 
marrow cell in groups exposed benzene increase 
during post-exposure period, (between 37% and 
58% at week 3 and week 6, respectively).  
Similarly there was a significant (P<0.05) 
increase in 8-OHdG concentration in bone 
marrow supernatant groups post exposed to 
benzene for 0 (3.75 ng/mg protein), 3 (3.90 
ng/mg protein) and 6 (4.50 ng/mg protein) weeks 
respectively, compared to the control (0.242 
ng/mg protein; Fig. 6). 

3.3 Effect of Benzene Exposure on Blood 
Film 

 

The histological study on blood film and bone 
marrow smear revealed different morphological 
changes in blood cells structures. The 
photomicrograph of blood film of benzene 
exposed group showed promyelocyte and 
myeloblast compared to normal control, 
promyelocyte (10-20 m) is slightly larger than a 
blast. Its nucleus, although similar to a 
myeloblast shows slight chromatin condensation 
and less prominent nucleoli. The cytoplasm 
contains striking azurophilic granules or             
primary granules. These granules contain 

 

 
 

Fig. 1. Effects of post treatment on red blood cell counts 
Each value is Mean ± SD. Bars with different alphabets (

a, b, c, d
) are significantly different from each other at 

p<0.05 
 

 
 

Fig. 2. Effects of post treatment duration of benzene on white blood cell counts 
Each value is Mean ± SD. Bars with different alphabets (a, b, c, d) are significantly different from each other at 

p<0.05 



 
 
 
 

Orisadiran et al.; AJI, 2(1): 1-10, 2019; Article no.AJI.52086 
 
 

 
5 
 

 
 

Fig. 3. Effects of post treatment duration of benzene on platelet counts 
Each value is Mean ± SD. Bars with different alphabets (

a, b, c, d
) are significantly different from each other at 

p<0.05 
 

 
 

Fig. 4. Effects of post treatment duration of benzene on liver 8-OHdG concentration 
Each value is Mean ± SD. Bars with different alphabets (a, b, c, d) are significantly different from each other at 

p<0.05 
 

myeloperoxidase, acid phosphatase, and 
esterase enzymes. Normally no promyelocytes 
are seen in the peripheral blood. Myelocytes (10-
18m) are slightly smaller than promyelocytes  
and have eccentric round-oval nuclei, often 
flattened along one side. The chromatin is fine 
but shows evidence of condensation. Nucleoli 
may be seen in early stages but not in the late 
myelocyte. 
 
The photomicrograph of blood films of the 
exposed group also shows hypersegmented 
neutrophil compared to normal control. 
Neutrophils are generally the most abundant 

white cell. They are round, are 10–14 µm                 
wide, and contain a lobulated nucleus with                  
two to four lobes connected by a thin chromatin 
thread. 
 

4. DISCUSSION 
 
A study has revealed that blood is the most 
important tissue in the body by which metabolic 
changes are reproduced [12], any changes in 
blood parameters and indices have always been 
considered to be the most reliable indicator of 
toxic effects of any substance, such as drugs and 
heavy metals. Changes in some haematological 



 
 
 
 

Orisadiran et al.; AJI, 2(1): 1-10, 2019; Article no.AJI.52086 
 
 

 
6 
 

parameters and indices were recorded in rats 
post expose to benzene. 
 
The principal function of WBCs as phagocytes is 
to defend the body against invading 
microorganisms or is xenobiotic by ingesting and 
destroying them and, hence, contributing to 
cellular mechanism [13]. The decrease in total 
WBC suggests a decrease in immune system in 
fighting foreign substances [14]. These findings 
were consistent with studies in which 

leucopoenia was shown to be the most sensitive 
effect on blood cells associated with benzene 
exposure [15,16]. A similar conclusion was 
reported by Tsai, et al. [17] in a large study on 
1,200 employees exposed to benzene. The 
mechanism underlying reduction in WBC is direct 
cytotoxicity of benzene metabolites on the 
production of WBC in the bone marrow. Benzene 
is known as immunotoxic and blood cell 
carcinogen, inducing anaemia, and blood formula 
modification [18]. 

 

 
 

Fig. 5. Effects of post treatment duration of benzene on bone marrow cell 8-OHdG 
concentration 

Each value is Mean ± SD. Bars with different alphabets (
a, b, c, d

) are significantly different from each other at 
p<0.05 

 

 
 
Fig. 6. Effects of post-treatment duration on bone marrow supernatant 8-OHdG concentration 

Each value is Mean ± SD. Bars with different alphabets (
a, b, c, d

) are significantly different from each other at 
p<0.05 



 
 
 
 

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Fig. 7. Photomicrograph of blood film of rat showing Normal Neutrophil (NN), Hypersegmented 
Neutrophil (HN), Promyelocyte (PM) and Myeloblast (MB)    (Leishman stain X1000) 

KEY: NN (Normal Neutrophil),  HN (Hypersegmented Neutrophil), PM (Promyelocyte), 
MB (Myeloblast) 

 

The RBC values showed a significant 
reduction in benzene post expose groups. 
The RBC reduction was duration dependent. 
This was consistent with the study of Sun, et al. 
[19] who reported a decrease in hematopoietic 
stem cells, reduced burst-forming unit-            
erythroid (BFU-E), committed progenitors 
granulocytes-erythroid-monocyte-megakaryocyte 
(CFU-GEMM) and granulocyte- macrophages 
(CFU-GM) progenitors in mice with subchronic 
benzene exposure. This result indicated that 
significant hematotoxicity was successfully 
induced by benzene exposure rat within 0, 3 or 6 
weeks of post-exposure. The observed reduction 
in RBC may be attributed to the cytotoxic effects 
of benzene. Oxidative stress may be induced by 
benzene with its effect on red cell membrane, 
this could possibly have accounted for the 
susceptibility of the red cell membrane to 
oxidative attack giving way to hemolysis. In 
studies carried out by Shakirov and Farkhutdinov 

[20], exposure or contact with chemicals in the 
oil-refining industry have been established to 
caused alterations in the red cell adenyl and 
blood monooxygenase system. They suggested 
that such an effect could alter the integrity of the 
red cell membrane to cause cellular haemolysis. 
Therefore, the result of this study agreed with 
their claim. 
 
This studied showed decreased in platelet counts 
in benzene post exposed rats. Megakaryocytes 
are large bone marrow cells which are 
responsible for platelet production [21]. 
Suppression of megakaryocytes or bone marrow 
suppression in benzene exposed rats decreased 
the production of platelets leading to thrombo-
cytopenia. The severity of suppression is directly 
proportional to post-exposure duration in 
benzene exposed rats in the present study. Low 
platelet count observed in benzene exposed rats 
suggested that the process of clot-formation will 



 
 
 
 

Orisadiran et al.; AJI, 2(1): 1-10, 2019; Article no.AJI.52086 
 
 

 
8 
 

be prolonged resulting in excessive loss of blood 
in the case of injury as reported by Gresele et al. 
[21].   

 
Reduction in the values of RBC, WBC and 
platelet content as recorded in this study is 
suggestive of anaemic conditions which agree 
with the report of Eyong, et al. [22] on the 
hematotoxicity of petroleum product. The 
haemopoietic system, in response to this likely 
anaemic condition, may have flooded the system 
with reticulocytes which can carry oxygen to 
meet the body's demand as earlier stated. 
Benzene is among other toxicants, suppresses 
the immune system, and causes disruption or 
suspension of haematopoiesis [23]; which 
corroborate the results in this study. It has also 
been established that the toxic constituents of 
benzene are activated in the bone marrow, 
where these substances exert cytotoxic effects 
that could be mediated through disturbance in 
DNA function [24]. The resultant bone marrow 
depression is characterized by inadequate 
production of red cell and other formed elements. 
This is in line with the findings in this study, as 
post exposure to benzene showed a significant 
reduction of RBC from the control value.  
 
When DNA is oxidized, a number of damage 
products such as base damage, sugar damage, 
and protein-DNA crosslinks are formed [25]. One 
of these products, 8-OHdG, has been proposed 
to be an indicator of oxidative damage in DNA 
both in vitro and in vivo. Our results showed a 
significant increase in liver and bone marrow 8-
OHdG levels compared to the control. This may 
be largely attributed to a high number of 
mitochondria and higher metabolism of liver cells 
[26]. Also, higher production of ROS in the liver 
cells is associated with a high density of 
mitochondria [27]. The quantity of 8-OHdG 
generated from DNA was dependent on the 8-
OHdG levels in the DNA, almost all 8-OHdG in 
the DNA was released as 8-OHdG by rat liver 
homogenates. Therefore, generation of 8-OHdG 
correlated with the degradation of DNA. The 
majority of benzene metabolism occurs in liver 
where cytochrome P-450 oxidizes benzene               
to phenol, catechol, hydroquinone and 
benzoquinone [27].  These phenolic metabolites 
and muconic acid are then transported from the 
liver to bone marrow. High accumulation of 
benzene and its metabolites over a long period in 
the bone marrow resulted in increased DNA 
lesion in benzene post exposed group. 
Furthermore, the chronic and progressive nature 
of benzene hematotoxicity suggests genomic 

reprogramming that would result in aberrant 
gene expression inducing extensive apoptosis in 
bone marrow resulting to increase generation of 
8-OHdG [28] as observed during the post-
treatment duration of benzene in the study  
 

5. CONCLUSION 
 

The present study has provided insight into the 
hematotoxicity of benzene and the degree of 
alteration of the integrity of haematological 
responses. Evidence from our study suggested 
that elevated levels of 8-OHdG in liver and bone 
marrow compare to control would be a sign of 
increased oxidative stress, impaired antioxidant 
defence or inadequate repair of oxidative 
damaged DNA.  
 

CONSENT  
 

It is not applicable. 
 

ETHICAL APPROVAL 
 
The protocol of the study was approved by the 
Local Ethical Committee for animal 
experimentation of the Faculty of Basic Medical 
Sciences, Ladoke Akintola University of 
Technology, Nigeria. 
 

ACKNOWLEDGEMENT  
 
We appreciate Sharphor Enterprises and Bolab 
Laboratories for their support throughout the 
period of this research. 
 
COMPETING INTERESTS 
 
Authors have declared that no competing 
interests exist. 
 

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© 2019 Orisadiran et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution 
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