Haemoglobin adducts of acrylonitrile and ethylene oxide in acrylonitrile workers, dependent on polymorphisms of the glutathione transferases GSTT1 and GSTM1

Thier, Ricarda, Lewalter, Jürgen, Kempkes, Manuela, Selinski, Silvia, Brüning, Thomas, & Bolt, Hermann M. (1999) Haemoglobin adducts of acrylonitrile and ethylene oxide in acrylonitrile workers, dependent on polymorphisms of the glutathione transferases GSTT1 and GSTM1. Archives of Toxicology, 73(4-5), pp. 197-202.

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Fifty-nine persons with industrial handling of low levels of acrylonitrile (AN) were studied. As part of a medical surveillance programme an extended haemoglobin adduct monitoring [N-(cyanoethyl)valine, CEV; N- (methyl)valine, MV; N-(hydroxyethyl)valine, HEV] was performed. Moreover, the genetic states of the polymorphic glutathione transferases GSTM1 and GSTT1 were assayed by polymerase chain reaction (PCR). Repetitive analyses of CEV and MV in subsequent years resulted in comparable values (means, 59.8 and 70.3 μg CEV/1 blood; 6.7 and 6.7 μg MV/1 blood). Hence, the industrial AN exposures were well below current official standards. Monitoring the haemoglobin adduct CEV appears as a suitable means of biomonitoring and medical surveillance under such exposure conditions. There was also no apparent correlation between the CEV and HEV or CEV and MV adduct levels. The MV and HEV values observed represented background levels, which apparently are not related to any occupational chemical exposure. There was no consistent effect of the genetic GSTM1 or GSTT1 state on CEV adduct levels induced by acrylonitrile exposure. Therefore, neither GSTM1 nor GSTT1 appears as a major AN metabolizing isoenzyme in humans. The low and physiological background levels of MV were also not influenced by the genetic GSTM1 state, but the MV adduct levels tended to be higher in GSTT1- individuals compared to GSTT1 + persons. With respect to the background levels of HEV adducts observed, there was no major influence of the GSTM1 state, but GST- individuals displayed adduct levels that were about 1/3 higher than those of GSTT1+ individuals. The coincidence with known differences in rates of background sister chromatid exchange between GSTT1- and GSTT1 + persons suggests that the lower ethylene oxide (EO) detoxification rate in GSTT1- persons, indicated by elevated blood protein hydroxyethyl adduct levels, leads to an increased genotoxic effect of the physiological EO background.

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ID Code: 77487
Item Type: Journal Article
Refereed: Yes
Keywords: Acrylonitrile, Ethylene oxide, Glutathione transferase (GST) polymorphisms, Haemoglobin adducts, glutathione transferase, hemoglobin, adult, aerobic metabolism, article, biological monitoring, blood sampling, enzyme metabolism, genetic polymorphism, genotoxicity, human, macromolecule, major clinical study, male, materials handling, occupational exposure, priority journal, sister chromatid exchange, Carcinogens, Disinfectants, Genotype, Hemoglobins, Humans, Polymerase Chain Reaction, Polymorphism, Genetic, Time Factors, Valine
DOI: 10.1007/s002040050606
ISSN: 0340-5761
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 1999 Springer-Verlag
Deposited On: 16 Oct 2014 01:37
Last Modified: 22 Jun 2017 23:01

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