title: Haemoglobin adducts of acrylonitrile and ethylene oxide in acrylonitrile workers, dependent on polymorphisms of the glutathione transferases GSTT1 and GSTM1.
abstract: 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 microg CEV/1 blood; 6.7 and 6.7 microg 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.
authors.affiliation: Institut für Arbeitsphysiologie an der Universität Dortmund, Germany. thier@arb-phys.uni-dortmund.de
authors.forename: R
authors.initials: R
authors.lastname: Thier
authors.forename: J
authors.initials: J
authors.lastname: Lewalter
authors.forename: M
authors.initials: M
authors.lastname: Kempkes
authors.forename: S
authors.initials: S
authors.lastname: Selinski
authors.forename: T
authors.initials: T
authors.lastname: Brüning
authors.forename: H M
authors.initials: HM
authors.lastname: Bolt
mesh_terms: D000181:Acrylonitrile / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism; D004202:Disinfectants / Q000378:metabolism; D005027:Ethylene Oxide / Q000378:metabolism*; D005838:Genotype; D005982:Glutathione Transferase / Q000145:classification / Q000235:genetics*; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016273:Occupational Exposure / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013997:Time Factors; D014633:Valine / Q000032:analysis
chemical_list: D002273:Carcinogens; D004202:Disinfectants; D006454:Hemoglobins; D005982:Glutathione Transferase; D014633:Valine; D005027:Ethylene Oxide; D000181:Acrylonitrile