|Year : 2014 | Volume
| Issue : 2 | Page : 97-99
Benzene, cytochrome, carcinogenesis: A topic in preventive toxicology
Wiwanitkit House, Bangkhae, Bangkok, Thailand
|Date of Web Publication||12-Dec-2014|
Wiwanitkit House, Bangkhae, Bangkok
Source of Support: None, Conflict of Interest: None
Benzene is a common chemical substance with confirmed toxicity to human beings. The benzene toxicity can be in either acute or chronic. Also, the carcinogenicity of benzene is confirmed. Hence, the control of benzene usage is a topic in preventive toxicology; however, this substance is still problematic in many industrialized settings. In this article, the author discusses benzene and cytochrome focusing on the carcinogenesis process. A further extrapolation on the aspects on preventive toxicology is also included.
Keywords: Benzene, cytochrome, carcinogenesis, preventive, toxicology
|How to cite this article:|
Wiwanitkit V. Benzene, cytochrome, carcinogenesis: A topic in preventive toxicology. Indian J Occup Environ Med 2014;18:97-9
|How to cite this URL:|
Wiwanitkit V. Benzene, cytochrome, carcinogenesis: A topic in preventive toxicology. Indian J Occup Environ Med [serial online] 2014 [cited 2019 Jul 18];18:97-9. Available from: http://www.ijoem.com/text.asp?2014/18/2/97/146900
| Introduction|| |
Benzene is a volatile aromatic substance that is widely used in industrial works. It is considered a common chemical substance leading to many toxic disorders. Both acute and chronic intoxications are described and are focused in present medicine.  In acute intoxication, nausea, vomiting, dizziness, headache, and death in the most severe cases are described. , In chronic exposure, several clinical manifestations including anemia and malignancy are mentioned. ,,
It is no doubt that a good control measure is needed for this problem. Regulation of benzene exposure becomes an important issue in occupational medicine and preventive toxicology. Indeed, several kinds of toxicities, such as hematotoxicity, hepatotoxicity, renotoxicity, neurotoxicity, and genotoxicity due to benzene exposure are described. , There are many studies on the toxicity of benzene with many new ones on the biomarkers and clinical biochemistry parameters alteration after exposure to benzene. Those studies are required for better understanding on the pathogenesis of benzene and further finding for preventive action.
In general toxicology, a response of human body to any intoxication can be expected. This is called detoxification system. A physiological action occurs in the liver, and the cytochrome system is an important biochemical system in human beings that responds to the toxic substance. Generally, drugs and other chemicals are usually metabolized in the liver based on the specific metabolizing enzyme system.  This is useful in detoxifying the toxic substance. On the other hand, the metabolites sometimes interact with cellular macromolecules leading to cellular injury and further pathological processes, including to carcinogenesis.  Based on the present knowledge, the pathobiological process via cytochrome system is widely described for its interrelationship to cancer development.  The indepth focus in genomics level is widely studied.  In this article, the author discusses benzene and cytochrome system, focusing on the carcinogenesis process. A further extrapolation on the aspects on preventive toxicology is also included.
Benzene, cytochrome, and carcinogenesis
It is no doubt that benzene can induce the toxicity to the exposed subjects. Similar to any toxic substances, the detoxifying of benzene via cytochrome system can be seen in normal physiology. Biologically, benzene is first metabolized via cytochrome P450 (primarily CYP2E1 in the liver). , The main metabolite is benzene-oxide, which can lead to the disturbance in the normal cytochrome system.  In vivo, benzene oxide-oxepin results in blocking one-electron oxidation by cytochrome P450 mono-oxygenase and finally leads to the formation of (E, Z)-muconaldehyde.  Accompanied with this process, a minor pathway leading to sym-oxepin oxide that can further repeat the mentioned process is also observed.  Of interest, the oxide-oxepin is the main substance that is mentioned for its DNA disturbance activity.  This is believed to be the primary process leading to genotoxicity and carcinogenesis. 
Hence, it is no doubt that there can be an interrelationship between the benzene and cytochrome. As already mentioned, the genetic mutations and polymorphisms within cytochrome system are focused as important factors leading to different responses to a toxic substance.  This concept can also be applied for explaining the pathobiology of benzene-induced malignancy. In a report by Ross et al., it is concluded that "Susceptibility to the toxic effects of benzene has been suggested to occur partly because of polymorphisms in enzymes involved in benzene metabolism, which include cytochrome P450 2E1. "
There are many new reports focusing on cytochrome and benzene. Most of them mention the possible relationship. Several cytochromes are studied and there is no conclusion yet. The examples of studies on some important cytochromes are further discussed.
CYP4F3A is a cytochrome that is widely studied for its relationship with benzene. It is reported that both benzene and metabolites resulted in the induction of CYP4F3A and DNA-PKcs.  This induction can be observed both in vivo and in vitro and this is the main pathogenesis of benzene hematotoxicity as well as leukemogenesis.  Therefore, it is assumed that CYP4F3A determination can be a good biomarker of benzene exposure. ,
CYP2E1 is another cytochrome that is focused on its relationship to benzene. There are many reports on CYP2E1 and benzene with different results. Most studies reported the null relationship between the polymorphic alleles of CYP2E1 and the metabolic activation of benzene, ,,, whereas a few mentioned a strong relationship. , Focusing on positive reports, , the CYP2E1 * 5B, *6, and *7B variants are mentioned as risk factors. However, not similar to the case of CYP4F3A, the CYP2E1 might not be a good biomarker for monitoring benzene exposure.
There are some other reports on other cytochromes and benzene. For example, a study in China reported that individuals with CYP2D6 c. 188 C/C, CYP2D6 c. 188 C/T, C/T, CYP1A1 MspIT/T, and c. 5639 T/T genotypes tend to be more susceptible to benzene toxicity. ,
Cytochrome and carcinogenesis of benzene: Aspect in preventive toxicology
It is no doubt that there are at least some relationships between cytochrome and carcinogenesis of benzene. Hence, there might be some applications on cytochrome determination as useful tool in preventive toxicology.
- Monitoring of cytochromes' activities can be helpful in determining the response to exposure. Higher induction of cytochrome might be the sign of high exposure. This monitoring is better than monitoring of metabolite because the monitoring of cytochrome activity is the direct measurement of response and toxicity to the human body. , In addition, there is no relationship between excreted metabolite in urine and cytochrome activity.  The explanation is the urine metabolite level is a cross-sectional measurement without any correlation to accumulation or deterioration of organ function due to that toxic substance
- Monitoring of genetic polymorphism of cytochromes can be a useful approach to judge for the risk of each individual in developing of cancer after exposure to benzene. At a same dosage of benzene exposure, one who has a risk allele might have more chance to further develop a cancer. Hence, there can be a good plan for each specific individual for decreasing his/her risk.
| References|| |
Zhang L, McHale CM, Rothman N, Li G, Ji Z, Vermeulen R, et al
. Systems biology of human benzene exposure. Chem Biol Interact 2010;184:86-93.
Goldstein BD. Benzene toxicity. Occup Med 1988;3:541-54.
Benzene. Rev Environ Contam Toxicol 1988;106:9-19.
Lauwerys R. Occupational chemical pollution and cancer. Arch Belg Med Soc 1979;37:337-84.
Schaffner F. Hepatic drug metabolism and adverse hepatic drug reactions. Vet Pathol 1975;12:145-56.
Kalow W. Pharmacogenetics in biological perspective. Pharmacol Rev 1997;49:369-79.
Golding BT, Barnes ML, Bleasdale C, Henderson AP, Jiang D, Li X, et al
. Modeling the formation and reactions of benzene metabolites. Chem Biol Interact 2010;184:196-200.
Monks TJ, Butterworth M, Lau SS. The fate of benzene-oxide. Chem Biol Interact 2010;184:201-6.
Bleasdale C, Cameron R, Edwards C, Golding BT. Dimethyldioxirane converts benzene oxide/oxepin into (Z, Z)-muconaldehyde and sym-oxepin oxide: Modeling the metabolism of benzene and its photooxidative degradation. Chem Res Toxicol 1997;10:1314-8.
Golding BT, Watson WP. Possible mechanisms of carcinogenesis after exposure to benzene. IARC Sci Publ 1999;150:75-88.
Ross D, Zhou H. Relationships between metabolic and non-metabolic susceptibility factors in benzene toxicity. Chem Biol Interact 2010;184:222-8.
Bi Y, Li Y, Kong M, Xiao X, Zhao Z, He X, et al
. Gene expression in benzene-exposed workers by microarray analysis of peripheral mononuclear blood cells: Induction and silencing of CYP4F3A and regulation of DNA-dependent protein kinase catalytic subunit in DNA double strand break repair. Chem Biol Interact 2010;184:207-11.
Zhao Z, He X, Bi Y, Xia Y, Tao N, Li L, et al
. Induction of CYP4F3 by benzene metabolites in human white blood cells in vivo
in human promyelocytic leukemic cell lines and ex vivo
in human blood neutrophils. Drug Metab Dispos 2009;37:282-91.
Hanioka N, Yamamoto M, Tanaka-Kagawa T, Jinno H, Narimatsu S. Functional characterization of human cytochrome P4502E1 allelic variants: In vitro
metabolism of benzene and toluene by recombinant enzymes expressed in yeast cells. Arch Toxicol 2010;84:363-71.
Dougherty D, Garte S, Barchowsky A, Zmuda J, Taioli E. NQO1, MPO, CYP2E1, GSTT1 and GSTM1 polymorphisms and biological effects of benzene exposure--a literature review. Toxicol Lett 2008;182:7-17.
Kim S, Lan Q, Waidyanatha S, Chanock S, Johnson BA, Vermeulen R, et al
. Genetic polymorphisms and benzene metabolism in humans exposed to a wide range of air concentrations. Pharmacogenet Genomics 2007;17:789-801.
Robert Schnatter A, Kerzic PJ, Zhou Y, Chen M, Nicolich MJ, Lavelle K, et al
. Peripheral blood effects in benzene-exposed workers. Chem Biol Interact 2010;184:174-81.
Piccoli P, Carrieri M, Padovano L, Di Mare M, Bartolucci GB, Fracasso ME, et al
. In vivo
CYP2E1 phenotyping as a new potential biomarker of occupational and experimental exposure to benzene. Toxicol Lett 2010;192:29-33.
Ulusoy G, Adali O, Tumer TB, Sahin G, Gozdasoglu S, Arinç E. Significance of genetic polymorphisms at multiple loci of CYP2E1 in the risk of development of childhood acute lymphoblastic leukemia. Oncology 2007;72:125-31.
Gu SY, Zhang ZB, Cao DZ, Wan JX, Gao XL, Jin XP, et al
. Genetic polymorphism of CYP-1A1, CYP2D6 and risks of chronic benzene poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2006;24:266-9.
Gu SY, Zhang ZB, Wan JX, Jin XP, Xia ZL. Genetic polymorphisms in CYP1A1, CYP2D6, UGT1A6, UGT1A7, and SULT1A1 genes and correlation with benzene exposure in a Chinese occupational population. J Toxicol Environ Health A 2007;70:916-24.
Lucas D, Ferrara R, Gonzales E, Albores A, Manno M, Berthou F. Cytochrome CYP2E1 phenotyping and genotyping in the evaluation of health risks from exposure to polluted environments. Toxicol Lett 2001;124:71-81.
Holyoke ED, Block GE, Jensen E, Sizemore GW, Heath H, Chu TM, et al
. Biologic markers in cancer diagnosis and treatment. Curr Probl Cancer 1981;6:1-68.