The Correlation between the Indoor Polluted Gases and Leukemia

Xinyuan Feng

1,† a

, Cenyun Guan

2,*,† b

and Zhijie Wu

3,† c

Pharmacy college, Wannan Medical College, Shou County, Anhui Province, China

University of California, Davis, California, U.S.A.

Guangdong Biguiyuan School, Foshan City, Guangdong Province, China

†

These authors contributed equally

Keywords: Air Pollution, Formaldehyde, Benzene, The Harmful Chemical Gases.

Abstract: With the developing of the society, the standards of human’s life are growing up. It is reasonable for people

to pursue a better living environment, which means they want to live in a clean, tidy and warm working place

to work and live. So plenty of people spent much money to decorate their homes. However, they were not

realized perhaps it is this kind of behavior that makes indoor air pollution more pollution sources and factors

affecting air quality which is harmful to their health. For example a large amount of formaldehyde, benzene

and other volatile organic compounds in the materials used for interior decoration will cause various health

hazards to the exposed population, including cancer. Besides, as the research at home and abroad, urban

residents spend about 80 to 90 percent of their time in the indoor environment everyday. So diseases caused

by harmful indoor gases arouse attention from the public and the government. More specifically, in 1990, the

US Environmental Protection Agency published a list of chemical substances that have bad effects to the

human body. The list of chemical substances covered four categories: particular matter, inorganic gases,

volatile organic compounds, and polycyclic aromatic hydrocarbons. Hind two kinds of material are indoor

harmful gas main component. So the research on the effect of harmful gases on human body is urgently

needed. However, China’s scientific research in this area is not sufficient, unable to adapt to the needs of

government management decisions and public health requirements. Therefore, the composition of various

chemicals indoor air and their effects on health are still very important topics at present. In this article we will

discuss the correlation between the harmful chemical gases, more specifically are formaldehyde and benzene,

and leukemia.

1 INTRODUCTION

The incidence of leukemia in China is (1-4) 100,000.

Among the death rates caused by malignant tumors,

leukemia ranks 6th (male) and 7th (female). Children

and adults under the age of 35 ranked first. The

incidence was slightly higher in males than in females

(1.81:1). The most common acute leukemia is acute

myeloid leukemia in adults and acute lymphoblastic

leukemia in children. The incidence of chronic

myeloid leukemia increases with age. The incidence

of chronic lymphocytic leukemia increases

significantly after the age of 50. Our country

leukaemia incidence of a disease and Asian other

https://orcid.org/0000-0001-5182-3494

https://orcid.org/0000-0003-2932-8897

https://orcid.org/0000-0003-0008-3531

country close, under euramerican country. In

particular, chronic lymphocytic leukemia is less than

5% of the total incidence of leukemia, while in

European and American countries, it accounts for

25%~30%.

In a 2021 study funded by the Natural Science

Foundation of Inner Mongolia Autonomous Region,

the relationship between toxic gases and blood

diseases was revealed through an analysis of blood

diseases induced by benzene exposure. Researchers

for patients admitted to hospital inspection, treatment

process and working condition of research for many

times, finally found benzene metabolites have

toxicity to hematopoietic stem/progenitor cells, not

only affect the bone marrow hematopoietic cell

426

Feng, X., Guan, C. and Wu, Z.

The Correlation between the Indoor Polluted Gases and Leukemia.

DOI: 10.5220/0011213900003443

In Proceedings of the 4th International Conference on Biomedical Engineering and Bioinformatics (ICBEB 2022), pages 426-433

ISBN: 978-989-758-595-1

proliferation, still can cause blood cells

differentiation and maturation of disorder, can lead to

uniparental cells, whole blood reduced, and even

induce aplastic anemia. Years of exposure to benzene

and organic solvents containing benzene are

associated with leukemia.Long-term exposure to

benzene and other harmful substances, considering

the incidence of leukemia is closelyrelated to benzene

exposure. Chemically-induced leukemia is more

common in AML.

In this paper, on the basis of the existing research,

the relationship between toxic gas and leukemia was

further explored. In addition, the researchers found

that toxic gases such as formaldehyde, benzene and

other chemical gases can also be released through

household furniture, carpets and wallpaper.

Therefore, this paper analyzes the relationship

between household air pollution and blood diseases.

Through the analysis of various types of blood

diseases and chemical substances, in-depth

understanding of the impact of toxic gases on human

body, and finally found that household pollution

gases such as formaldehyde, benzene and leukemia

have a high correlation.

2 BACKGROUND OF HARMFUL

GASES EMITTED BY

BUILDING MATERIALS

2.1 The Source of the Chemical Gases

The source of indoor polluted gases are mainly from

the fuel burning, smoking, daily using, building

materials and decoration materials. Burning material

are natural gases, coal and plant leaves. When burned,

these substances produce carbon oxides, nitrogen

oxides, sulfur oxides, and polycyclic aromatic

hydrocarbons. The indoor harmful gases produced by

smoking are nicotine, nitrogen dioxide, carbon

dioxide. Besides, chemical gases are mainly from the

building and decoration materials, for example,

decorate plank, coating, cementing compound.

Which is worth mentioning, furniture, carpets and

wallpaper also emit chemical gases.

2.2 The Types of the Indoor Chemical

Pollution and the Diseases May

Bring

Table 1: Classification of indoor hazardous gases and

possible diseases.

Pollutant

Critical outcome(s) for

uideline definition

Benzene

Acute myeloid leukaemia

(sufficient evidence on

causalit

Formaldeh

de Sensor

irritation

Naphthalene

Respiratory tract lesions

leading to inflammation and

malignanc

in animal studies.

Radon Lung cance

Trichloroethylene

Carcinogenicity with the

assumption of genotoxicut

Tetrachloroethylene

Effect in the kidney

indicative of early renal

disease and impaired

erformance

Polycyclic aromatic

hydrocarbons

Lung cancer

The table1 is from an article which is published

by WTO (OMS 2000), which discuss about the main

types of the pollution gases and the disease they may

cause. Atpresent,the international classification

standards for carcinogens are formulated by the

International Institute under the jurisdiction of the

United States. It mainly covered four stages: A, B, C

and D, among them A represented that a well-

documented carcinogenicity in humans. According to

the report published by IARC in 2008,which showed

that formaldehyde and benzene were belonging to the

class A carcinogen .So in this article we will discuss

the correlation between the formaldehyde ,benzene

and leukemia.

2.3 The Introduction about the

Formaldehyde and Benzene

2.3.1 General Description of the Benzene

Benzene is an aromatic compound with a single six-

member unsaturated carbon ring. This is a colorless

transparent liquid with a special aroma, which is able

to rapid evaporation at room temperature. Inhalation

of high concentration of benzene vapor in a very short

period of time can caused acute benzene poisoning,

excitement or intoxication, accompanied by

symptoms of mucosa irritation (OMS 2000).

The Correlation between the Indoor Polluted Gases and Leukemia

427

2.3.2 Indoor Sources of the Benzene

Indoor benzene often from decoration materials,

furniture, garbage, storage appliances and human

activities. At the same time, indoor concentration also

affected by the frequency and area of indoor and

outdoor air circulation. In the United States,

everybody absorbs indoor benzene each day on

average was between 180 and 1300μg (WHO 2000).

In general, the amount of benzene emitted from food

is very tiny. In addition to normal source of benzene,

such as decoration materials, cigarette smoke is also

a vital source of benzene in indoor air, which is

harmful to the human’s lung.

2.3.3 Hazards of Benzene to Human Body

To the mechanism of action of benzene toxicity, it

always has two types. At the high level benzene

concentration, it just like a narcotic that depress the

central nervous system and causes cardiac

sensitization and finally lead to the leukemia. More

specifically, benzene is genetically toxic, leading to

the missing of the chromosomes long arms. This

change may bring to myelodysplastic syndrome,

which is the start of the leukemia. Benzene can also

causes mutations in alleles, in this situation, bone

marrow cells will experience mutations and then

becomes to leukemia (Wang et al 1998). The bad

effects of the benzene under low-level is lack of the

suitable animal model, so we will not discuss it.

There are plenty of reports of people deaths from

inhaling high concentrations of benzene. Human may

die immediately or die several hours later in this

situation. When concentration between the 300 and

3000ppm (CRONIN, and Herbert 1924), Flury,1928,

Midzenski, et al, 2010),the symptoms are always

shown as the speaking problems, headaches,

dizziness, insomnia (OMS 2000).

Benzene metabolites also trigger chromosomal

aberrations. The carcinogenic of action of benzene

has relationship with its genotoxic effects and the

critical health outcomes are bloody dyscrasias and

leukemia, especially becomes to the acute myeloid

leukemia (OMS 2000).

2.4 The Introduction of the

Formaldehyde

2.4.1 General Description of the

Formaldehyde

Formaldehyde is a naturally occurring compound

with the formula CH2O.The pure compound is

colorless, flammable gas at room temperature and has

a pungent odor. Which is worth mentioning,

formaldehyde is a versatile, reactive substance, in

common use to the industry because of its low prize

and ease of production. So it is familiar and can be

easily found in our daily-used products.

2.4.2 The Source of the Indoor

Formaldehyde

Major source of formaldehyde is the building

materials and consumer products (Salthammer,

Mentese and Marutzky 2010, Kelly, Smith, Satola

1999). It is always found in the composite wood

products, furniture and so on.

The possible routes of exposure to formaldehyde

are inhalation, ingestion and dermal absorption.

Human can be exposed to formaldehyde by breathing

air containing off gassed formaldehyde.

2.4.3 The Health Effect of the

Formaldehyde

In recent years, formaldehyde has come under

increased scrutiny of its potential negative health

effects. After acute and short-term exposure to

formaldehyde at indoor levels, people may have

sensory irritation to the eyes and upper airways, lung

discomfort and finally eczema (OMS 2000).

The meta-analysis on account of the highest

exposure levels reported that formaldehyde can cause

especially myeloid leukemia (Salthammer, Mentese

and Marutzky 2010). Firstly, blood will deliver the

formaldehyde to the bone marrow, and in bone

marrow would lead to origination in a stem.

Secondly, as a portion of the bone marrow stem and

progenitor cells circulate in the peripheral blood, they

may be started by formaldehyde which was absorbed

into the blood.

Lastly, the starts of the initial multifunctional

stem cells provided within the nasal mucosa could

occur, followed with transport to the bone marrow.

3 THE INTRODUCTION OF

LEUKEMIA AND ITS

PATHOGENESIS

Nowadays, leukemia is separated into 4 main types

based on acute or chronic diseases and myeloid or

lymphocytic diseases.

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

428

3.1 Acute Myeloid (or Myelogenous)

Leukaemia (AML)

Acute myeloid leukemia is a disease caused by an

increasing number of myeloid cells in the marrows

and their maturation is repressed, which caused

hematopoietic insufficiency, such as

granulocytopenia, thrombocytopenia, or anemia,

with or without the leukocytosis.

Through molecular pathogenesis, Acute myeloid

leukemia is related to specific cytogenetic lesions.

Through the research, the alteration of AML1-

CBFb is one of the major reasons which caused the

AML. The DNA-binding subunit of AML1-CBFb, a

transcription factor that is the essential for normal

development of the hematopoietic system. Through

the AML associated chromosomal rearrangement

inv(16) or its variant t(16;16) targets CBFb, AML1-

CBFb is the target of the t(12;21) translocation in

several rare translocations in AML, making it become

the most common target of chromosomal

rearrangements in human leukemia.

Figure 1: The AML1-CBFb Transcription Factor.

Through figure 1, the CBFb and the AML1 and

Coactivators can be normally pass through to the

target gene. However, the DNA-binding and CBFb-

interaction domains, form the C-terminal portion of

the 821 genes (ETO) on chromosome 8 and the

corepressor complex caused the failure to activate

transcription. In the inv(16) (p13;q22) and the

t(16;16)(p13;q22), mutations caused the CBFb

subunit of the core binding-factor complex on

chromosome 16q22 to be fused to the smooth-muscle

myosin heavy-chain gene MYH11 on chromosome

16p13.32 and make a product of CBFb-MYH11

chimeric, which caused the inactivation of AML1 and

fail to be a transcript. meric, which caused the

inactivation of AML1 and fail to be

transcript(Appelbaum, et al 1999).

3.2 Acute Lymphocytic (or

Lymphoblastic) Leukaemia (ALL)

Acute lymphocytic leukemia (ALL) is a lymph

cancer, and its characters can be seen as the

development of large numbers of immature

lymphocytes. The ALL influences the bone marrow

and the blood. The ALL can be developed very fast

and it can be easy to cause death without appropriate

treatment.

Acute lymphocytic leukemia (ALL) is caused by

several reasons.

1) Idiopathic (most of ALL)

2) Haematological disorders (Underlying)

3) Chemicals and Drugs

4) Ionization radiation

5) Viruses (HTLV-I)

6) Hereditary/ Genetic conditons

Most of the ALL is Idiopathic which means there

are not any distinct causes and there is still no clear

answer as to what causes ALL. Chemicals and Drugs

and Ionization radiation can be also defined as

environmental factors.

Through the viruses (HTLV I) can also be caused

the ALL, the pathological mechanism of

transforming retroviruses HTLV-I is unclear, but

there are only 2 ways to caused the disease of ALL,

which is encoding oncogenes that mediate viral

transformation or disrupt cellular gene expression as

a byproduct of proviral integration.

The last reason is the hereditary/genetic

conditions, this reason is also complex without any

clear evidence that can be used to prove how it caused

acute lymphocytic leukemia (Gatza, Watt and

Marriott 2003).

3.3 Chronic Myeloid (or Myelogenous)

Leukaemia (CML)

Chronic myeloid leukemia (CML) is caused by the

bone marrow hematopoietic stem cells growing in the

form of clonal proliferation and became a malignant

tumor. Chronic myeloid leukemia is asymptomatic in

the early stages, CML does not become apparent until

The Correlation between the Indoor Polluted Gases and Leukemia

429

the middle and even ultimately leads to death in the

late stage.

The pathological mechanism can be attributed to

the altered function of the 2 genes in the Ph

transcription. The genes are ABL and BCR genes are

changed and caused the CML. The BCR gene is on

chromosome number 22. The ABL gene is on

chromosome number 9. The ABL part in the chimeric

protein is invariably constant, but the BCR gene

varies greatly. The ABL gene has the transforming

principle and the size of the BCR sequence can

determine the phenotype of the disease.

Through the research, the BCR-ABL is the

combination of genes ABL and BCR which are the

gene sequence and found in the abnormal

chromosome 22 of people with chronic myeloid

leukemia. The mutation in the BCR-ABL can affect

the organization of cell membrane and cytoskeleton

and also it can be caused the communication between

cells and the environment and disturb the response by

the cells. Therefore, the mutated BCR-ABL protein

caused not just a change in a single path, it can also

change in multiple paths (shown in figure 2). As a

result, it caused chronic myeloid leukemia (Melo

2001)

Figure 2: The signaling pathways shown in the activated

BCR-ABL.

3.4 Chronic Lymphocytic Leukaemia

(CLL)

Chronic lymphocytic leukemia (CLL) is most

common in B-cell, the feature is the accumulation of

CD5 + B cells in the blood, bone marrow, lymph

nodes, and spleen. The early stage of chronic

lymphocytic leukemia (CLL) does not have any

symptoms but may show symptoms in the middle and

later stages.

The mechanism of chronic lymphocytic leukemia

(CLL) is unclear, but it can be identified by the

accumulation of B-cell, and the trend of B-cell caused

the lymphadenopathy, liver and spleen enlargement,

anemia and bleeding, and complication (Olsson, et al

2007).

4 BENZENE AND

FORMALDEHYDE HARMFUL

TO HUMAN BODY

4.1 Metabolism of Formaldehyde and

Benzenes

4.1.1 Metabolic Process and Products of

Formaldehyd

Formaldehyde (chemical formula HCHO) is the

simplest aldehyde molecule and is toxic. It has been

listed as a Class I carcinogen by the International

Agency for Research on Cancer of the World Health

Organization on October 27, 2017.The metabolism of

formaldehyde in the human body mainly depends on

the catalysis of enzymes. The enzymes that degrade

formaldehyde are mainly ethanol dehydrogenase I

distributed in pyramidal and granulocytes of

hippocampal formation, cerebral cortex and vascular

epithelial tissue of brain; ethanol dehydrogenase III

existing in various tissues and organs; and

dehydrogenase II, the most active of aldehyde

dehydrogenase which is mainly distributed in cell

mitochondria. Formaldehyde is degraded to formic

acid, which is directly discharged from the kidney or

exhaled out of the body through oxidation to CO2

(Tulpule, Hohnholt, and Dringen 2013). This was

confirmed in experiments: Zhang Ruiwen et al.

(Zhang and Wang 1990) studied the metabolic

process of formaldehyde in red blood cells based on

the ability of separation of formaldehyde

dehydrogenase in human red blood cells and liver and

found that formaldehyde metabolizes into formic acid

in red blood cells, and the higher the initial

formaldehyde concentration, the slower the

metabolic process and the lower the metabolic rate.

4.1.2 Metabolic Process and Products of

Benzenes

Benzene, toluene and xylene (collectively referred to

as the three benzenes) are the most representative

benzenes. They are gaseous at room temperature and

can enter the human body through multiple channels

such as respiratory tract, gastrointestinal tract, skin

and mucous membrane, thus affecting human health.

Among them, benzene was listed as a Class I

carcinogen by the International Agency for Research

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430

on Cancer of the World Health Organization on

October 27, 2017, and toluene and xylene were listed

as Class III carcinogens.

Some benzene substances in the human body can

be directly discharged through urine, while the

benzene substances that are not discharged are first

oxidized to epoxy benzene under the action of

cytochrome P450 monooxygenase in the liver, and

the epoxy benzene continues to combine with

glutathione to form S-phenylmercapturic acid

(SPMA); or continue to be metabolized into phenol,

catechol and others, which are discharged in the form

of glucosidic acid or sulfate conjugates; or are

oxidized to adipic acid. This has also been confirmed

by experiments: the study of Wan Lingli et al. (Wan,

Zheng, pan, Ke 2021) found that six metabolites such

as S-phenylmercaptouric acid (SPMA) and hippuric

acid (HA) were much higher in people chronically

exposed to benzenes than those not exposed.

4.2 Effects of Formaldehyde and

Benzenes on Humanbody

4.2.1 Liver

Formaldehyde and benzenes can affect the expression

level of metabolism related genes in the liver (Chen,

et al 2009), reduce the ability of liver tissue to

scavenge oxygen free radicals and antioxidants,

decrease trace elements in liver tissue, cause liver

injury, and cause inflammatory changes and even

tumor in the liver.

4.2.2 Skin

Formaldehyde and benzenes can affect the content of

ceramide in basic lipid components of skin (Nardo,

Di, et al 2007), causing contact dermatitis and

mucosal irritation. Irritation of human skin by

formaldehyde and benzenes produces discoloration,

redness, hardening and skin scaling. The lesions

usually appear first on the hand and forearm as

papules; rashes may appear on other parts of the body

as fused papules, with erythema in some areas,

followed by desquamation, and exfoliative dermatitis

on hands and feet in severe cases.

4.2.3 Respiratory Tract

Formaldehyde and benzenes inhibit the formation of

nasal cilia, especially the front end of nasal cilium,

which has a mutagenic and damaging effect on DNA

of human bronchial cells, and cause irritation of the

human nose and upper respiratory tract (Ballenger

2010), thus increase the incidence of respiratory

symptoms, chronic rhinitis, bronchitis, pneumonia

and abnormal pulmonary function.

4.3 The Correlation between Toxic

Gases and Leukemia

Leukemia is a type of malignant tumor of the vascular

system, and although its pathology is still not fully

understood, the current understanding is that the

mechanism of its occurrence has some correlation

with the environment, genetic factors, and other

elements. Currently, the relationship between toxic

gases and leukemia is receiving increasing interest

from the scientific community, with critical research

needed to confirm this theory and determine methods

of decreasing people’s exposure to toxic gases and

thereby reducing the rate of disease occurrence.

Research clearly shows leukemia occurrence rates to

be related to benzene, formaldehyde, chlorine, and

over 100 other kinds of volatile, toxic gases and

pollutants. Benzene and its metabolites, along with

other toxic gases, damage the bone marrow through

the body’s immune response, resulting in leukemia

(Jiang, Gao 2014).

Through related studies, it has been found that

people with a history of smoking have an elevated

occurrence rate of leukemia, because burning tobacco

releases large amounts of toxic gases, including

benzene as well as radioactive chemical compounds

and nitrosamine, of which benzene and the BTEX

family of compounds make up a very large

proportion. Benzene can increase the occurrence of

leukemia by any of the following methods: 1)

Benzene and its metabolites, including hydroquinone

and benzoquinone, produce oxygen free radicals as a

product of their metabolism, which can harm the

DNA of bone marrow cells; 2) It can induce changes

in chromosomal structure, such as chromosome

deletion or translocation; 3) Benzene exposure can

lead to IL6 and cytochrome P450 2E1 methylation,

causing cells to show genetic changes. As for

smokers, over 80% of benzene exposures are due to

tobacco smoke, and the daily benzene intake of

smokers is 6-10 times that of non-smokers. The

dosage of benzene in every pack of cigarettes smoked

can reach 1.5mg, raising the benzene intake, and the

occurrence of leukemia, in smokers far above that of

non-smokers (Gross and Paustenbach 2017).

In the building renovation process, paints,

composite materials, furniture, and other materials

can release benzene, formaldehyde, chlorine, and

over 100 other kinds of volatile, toxic gases. Among

these, formaldehyde, a colorless, highly oxidizing

irritant with a strong odor, is most prevalent.

The Correlation between the Indoor Polluted Gases and Leukemia

431

Formaldehyde has a multitude of pathogenic

mechanisms, including its tendency to break apart the

DNA of bone marrow cells and form DNA-protein

cross-links, thereby producing severe genotoxicity.

After a person comes into contact with formaldehyde-

containing air, their microRNA expression may be

lowered, leading to cancer. Related studies show that

formaldehyde concentration and whole blood

viscosity have a positive correlation, and that higher

formaldehyde concentrations cause more oxidative

damage to the membrane of red blood cells. The

correlation between formaldehyde concentration and

whole blood viscosity is lower in females than in

males of the same age group. Overall, formaldehyde

exposure is related to increased occurrence of

leukemia in adults (Wei, et al 2017).

Vehicle exhaust emissions release many types of

toxic gases, including cancer-causing PM2.5,

benzene, and many other polycyclic aromatic

hydrocarbons (PAH), and may also lead to the

occurrence of leukemia. Among these, PM2.5 has a

small particle size with relatively large surface area,

and remains in the air for long periods of time,

adsorbing large quantities of free radicals and heavy

metal ions. It also has an effect on bronchial epithelial

cells, stimulating inflammation in the respiratory

system due to the release of oxygen free radicals, and

subsequently inducing an oxidative stress reaction.

Under the effects of oxidative damage, the lipid layer

of the cell membrane undergoes oxidation, leading to

calcium overload in the cell, and thereby destroying

the functionality of the mitochondria. This forms a

vicious cycle wherein free radicals induce calcium

overload in the cell, and ultimately leads to the death

of the cell. Therefore, PM2.5 also has a very high

correlation with the occurrence of leukemia (Teras, et

al 2019).

5 CONCLUSIONS

Through the study of multiple papers, we find that

about three directions reasons may cause leukemia:1)

a history of smoking is associated with a higher

incidence of leukemia, mainly through benzene and

nitrous acid to change the body to increase the risk of

leukemia. 2) In the building construction, such as oil

paint and composite materials, they emit

formaldehyde is the most common toxic gas which

lead the whole blood viscosity rise up, finally cause

leukemia. 3)Car exhaust emissions are mainly

PM2.5, which can absorb and carry a large number of

free radicals, induce stress response, and ultimate

destroy mitochondrial function, leading to bronchial

epithelial cells, it is the primary pathogenesis of

leukemia.

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