Effects of variation in detoxification rate on dose monitoring through adducts

Abstract

1 Föst et al. ( Human & Experimental Toxicology 1991; 10: 25) have shown that ethylene oxide (EO) added to human blood gave rise to a higher level of adducts to haemoglobin (Hb) when the donors were deficient in an erythrocytic glutathione S-transferase (GST, later found to be GST-theta) than in blood from persons pos sessing this enzyme, and drew the conclusion that this polymorphism in detoxification rendered Hb adducts less suitable for biological monitoring.

2 By fitting a kinetic model to the data, the present study shows that the Hb adduct level gives a correct measure of the dose (concentration integrated over time) rele vant to risk estimation.

3 It does illustrate, however, the importance of knowing an individual's detoxification efficiency, when Hb adduct measurements are used to assess environmen tal exposure, for example in occupational surveillance.

Keywords

ethylene oxide hemoglobin adducts GST-poly morphism GST-theta dose

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References

Föst U. , Hallier E. , Ottenwälder H. , Bolt HM & Peter H.

Distribution of ethylene oxide in human blood and its implications for biomonitoring

Human and Experimental Toxicology 1991; 10: 25-31.

Schröder K. , Hallier E. , Peter H. & Bolt HM Dissociation of a new glutathione S-transferase activity in human erythrocytes. Biochemical Pharmacology 1992; 43: 1671-4.

Ehrenberg L. , Moustacchi E. & Osterman-Golkar S. Dosimetry of genotoxic agents and dose-response relationships of their effects. Mutation Research 1983; 123: 121-82.

Föst U. Chemisch-analytische Möglichkeiten für ein "Biologisches Monitoring" bei Exposition gegenüber Vinylchlorid und Ethylenoxid. Ph.D. Thesis, Dortmund, 1991.

Leutbecher M. , Langhof T. , Peter H. & Föst U. Ethylene oxide: Metabolism in human blood and its implication to biological monitoring. Archives of Toxicology 1992; Suppl. 15: 289.

Hallier E. , Langhof T. , Dannappel D. et al. Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes. Archives of Toxicology 1993; 67 : 173-8.

Segerbäck D. Alkylation of DNA and hemoglobin in the mouse following exposure to ethene and ethene oxide. Chemical-Biological Interactions 1983; 45: 139-51.

Walker V. , Fennell T. , Upton P. , MacNeela J. & Swenberg J. Molecular dosimetry of DNA and hemoglobin adducts in mice and rats exposed to ethylene oxide. Environmental Health Perspectives 1993; 99: 11-17.

Granath F. , Ehrenberg L. & Törnqvist M. Degree of alkylation of macromolecules in vivo from variable exposure . Mutation Research 1992; 284: 297-306.

10.

Duus U. , Osterman-Golkar S. , Törnqvist M. , Mowrer J. , Holm S. & Ehrenberg L. Studies of determinants of tissue dose and cancer risk from ethylene oxide exposure. In: Proc. Symp. Management of Risk from Genotoxic Substances in the Environment (L. Freij, Ed.), Swedish National Chemicals Inspectorate , Solna, Sweden, 1989 ; 141-53 .

11.

Törnqvist M. , Osterman-Golkar S. , Kautiainen A. , Näslund M. , Calleman CJ & Ehrenberg L. Methylations in human hemoglobin. Mutation Research 1988 ; 204: 521-9.

12.

Seidegård J. , Pero RW , Miller DG & Beattie EJ A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. Carcinogenesis 1986; 7: 751-3.

13.

Strange RC , Matharoo B. , Faulder GC et al. The human glutathione S transferases: a case control study of the incidence of the GST10 phenotype in patients with adenocarcinoma . Carcinogenesis 1991; 12 : 25-8.

14.

Hoel DG , Kaplan NL & Anderson MW Implication of nonlinear kinetics on risk estimation in carcinogenesis . Science 1983; 219 : 1032-7.

15.

Törnqvist M. , Svartengren M. & Ericsson CH Methylations in hemoglobin from monozygotic twins discordant for cigarette smoking: hereditary and tobacco-related factors . Chemical-Biological Interactions 1992; 82: 91-8.