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Spontaneous Production of Glutathione-Conjugated Forms of 1,2-Dichloropropane: Comparative Study on Metabolic Activation Processes of Dihaloalkanes Associated with Occupational Cholangiocarcinoma
Joint Authors
Toyoda, Yu
Suzuki, Hiroshi
Takada, Tappei
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-05-07
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Recently, epidemiological studies revealed a positive relationship between an outbreak of occupational cholangiocarcinoma and exposure to organic solvents containing 1,2-dichloropropane (1,2-DCP).
In 1,2-DCP-administered animal models, we previously found biliary excretion of potentially oncogenic metabolites consisting of glutathione- (GSH-) conjugated forms of 1,2-DCP (GS-DCPs); however, the GS-DCP production pathway remains unknown.
To enhance the understanding of 1,2-DCP-related risks to human health, we examined the reactivity of GSH with 1,2-DCP in vitro and compared it to that with dichloromethane (DCM), the other putative substance responsible for occupational cholangiocarcinoma.
Our results showed that 1,2-DCP was spontaneously conjugated with GSH, whereas this spontaneous reaction was hardly detected between DCM and GSH.
Further analysis revealed that glutathione S-transferase theta 1 (GSTT1) exhibited less effect on the 1,2-DCP reaction as compared with that observed for DCM.
Although GSTT1-mediated bioactivation of dihaloalkanes could be a plausible explanation for the production of reactive metabolites related to carcinogenesis based on previous studies, this catalytic pathway might not mainly contribute to 1,2-DCP-related occupational cholangiocarcinoma.
Considering the higher catalytic activity of GSTT1 on DCM as compared with that on 1,2-DCP, our findings suggested differences in the activation processes associated with 1,2-DCP and DCM metabolism.
American Psychological Association (APA)
Toyoda, Yu& Takada, Tappei& Suzuki, Hiroshi. 2017. Spontaneous Production of Glutathione-Conjugated Forms of 1,2-Dichloropropane: Comparative Study on Metabolic Activation Processes of Dihaloalkanes Associated with Occupational Cholangiocarcinoma. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-9.
https://search.emarefa.net/detail/BIM-1196676
Modern Language Association (MLA)
Toyoda, Yu…[et al.]. Spontaneous Production of Glutathione-Conjugated Forms of 1,2-Dichloropropane: Comparative Study on Metabolic Activation Processes of Dihaloalkanes Associated with Occupational Cholangiocarcinoma. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-9.
https://search.emarefa.net/detail/BIM-1196676
American Medical Association (AMA)
Toyoda, Yu& Takada, Tappei& Suzuki, Hiroshi. Spontaneous Production of Glutathione-Conjugated Forms of 1,2-Dichloropropane: Comparative Study on Metabolic Activation Processes of Dihaloalkanes Associated with Occupational Cholangiocarcinoma. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-9.
https://search.emarefa.net/detail/BIM-1196676
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1196676