Possible impact of human CYP2E1 polymorphisms on the metabolism of acrylonitrile

Thier, Ricarda, Lewalter, Jürgen, Selinski, Silvia, & Bolt, Hermann M. (2002) Possible impact of human CYP2E1 polymorphisms on the metabolism of acrylonitrile. Toxicology Letters, 128(1-3), pp. 249-255.

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Abstract

Case reports of human accidental poisonings point to significant individual differences in human acrylonitrile metabolism and toxicity. A cohort of 59 persons with industrial handling of low levels of acrylonitrile has repetitively been studied from 1994 through 1999 as part of a medical surveillance programme. The analyses included adduct determinations of N-terminal N-(cyanoethyl)valine in haemoglobin and genotypings of the following cytochrome P-450 2E1 (CYP2E1) polymorphisms: G-1259C and C-1019T (two subjects heterozygous), A-316G (three subjects heterozygous), T-297A (15 subjects heterozygous), G-35T (eight subjects heterozygous), G4804A (two subjects heterozygous), T7668A (six subjects heterozygous). N-(Cyanoethyl)valine adduct levels were, if any, only slightly influenced by smoking and mainly determined by the external acrylonitrile exposures. The individual means and medians of N-(cyanoethyl)valine levels over the entire observation period were compared with the CYP2E1 variants (Wilcoxon rank sum test). No influences of the investigated CYP2E1 polymorphisms on the N-(cyanoethyl)valine levels appeared at the 5% level. However, there was a trend, at a level of P≃0.1, pointing to higher acrylonitrile-specific adduct levels in persons with the A-316G mutation. Higher adduct levels would be compatible with a slower CYP2E1-mediated metabolism of acrylonitrile and with lower extents of toxification to cyanide.

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ID Code: 77490
Item Type: Journal Article
Refereed: Yes
Keywords: Acrylonitrile, CYP2E1 polymorphisms, Haemoglobin adducts, N-(Cyanoethyl)valine, cyanide, cytochrome P450 2E1, hemoglobin derivative, valine, amino terminal sequence, article, assay, cohort analysis, controlled study, detoxification, enzyme polymorphism, female, genotype, heterozygosity, human, intoxication, male, periodic medical examination, priority journal, smoking, Cohort Studies, Cytochrome P-450 CYP2E1, DNA, Humans, Occupational Exposure, Polymerase Chain Reaction, Polymorphism, Genetic, Polymorphism, Restriction Fragment Length, Statistics, Nonparametric
DOI: 10.1016/S0378-4274(01)00546-X
ISSN: 0378-4274
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2002 Elsevier Science Ireland Ltd.
Deposited On: 15 Oct 2014 22:40
Last Modified: 15 Oct 2014 22:40

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