Benzo(a)pyrene diolepoxide adducts to albumin in workers exposed to polycyclic aromatic hydrocarbons

Association with specific CYPIAI, GSTMI, GSTPI and EHPX genotypes

R. Pastorelli, A. Cerri, M. Rozio, M. Dell'Omo, G. Muzi, G. Abbritti, R. Fanelli, L. Airoldi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We investigated whether the presence of (+)-anti-benzo(a)pyrene diolepoxide adducts to serum albumin (BPDE-SA) among workers exposed to benzo(a)pyrene (BaP) and unexposed reference controls was influenced by genetic polymorphisms of cytochrome P4501A1 (CYP1A1), microsomal epoxide hydrolase (EHPX), glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), all involved in BaP metabolism. Exposed workers had significantly higher levels of adducts (0.124 ± 0.02 fmol BPT mg-1 SA, mean ± SE) and a higher proportion of detectable adducts (40.3%) than controls (0.051 ± 0.01 fmol BPT mg-1 SA; 16.1%) (p = 0.014 and p = 0.012). Smoking increased adduct levels only in occupationally exposed workers with the GSTM1 deletion (GSTM1 null) (p = 0.034). Smokers from the exposed group had higher adduct levels when they were CYP1A1 *1/*1 wild-type rather than heterozygous and homozygous for the variant alleles (CYP1A1 *1/*2 plus *2/*2) (p = 0.01). The dependence of BPDE-SA adduct levels and frequency on the CYP1A1 *1/*1 genotype was most pronounced in GSTM1-deficient smokers. Exposed workers with GSTM1 null/GSTP1 variant alleles had fewer detectable adducts than those with the GSTM1 null/GSTP1*A wild-type allele, supporting for the first time the recent in vitro finding that GSTP1 variants may be more effective in the detoxification of BPDE than the wild-type allele. Logistic regression analysis indicated that occupational exposure, wild-type CYP1A1*1/*1 allele and the combination of GSTM1 null genotype + EHPX genotypes associated with predicted low enzyme activity were significant predictors of BPDE-SA adducts. Though our findings should be viewed with caution because of the relatively limited size of the population analysed, the interaction between these polymorphic enzymes and BPDE-SA adducts seems to be specific for high exposure and might have an impact on the quantitative risk estimates for exposure to polycyclic aromatic hydrocarbons.

Original languageEnglish
Pages (from-to)357-374
Number of pages18
JournalBiomarkers
Volume6
Issue number5
DOIs
Publication statusPublished - 2001

Fingerprint

Benzo(a)pyrene
Polycyclic Aromatic Hydrocarbons
Albumins
Cytochromes
Genotype
Serum Albumin
Alleles
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Epoxide Hydrolases
Detoxification
Enzyme activity
Genetic Polymorphisms
Enzymes
Occupational Exposure
Population Density
glutathione S-transferase M1
Polymorphism
Metabolism
Regression analysis
Logistics

Keywords

  • Benzo(a)pyrene diolepoxide adducts
  • Genetic polymorphism
  • Occupational exposure

ASJC Scopus subject areas

  • Biotechnology
  • Toxicology

Cite this

Benzo(a)pyrene diolepoxide adducts to albumin in workers exposed to polycyclic aromatic hydrocarbons : Association with specific CYPIAI, GSTMI, GSTPI and EHPX genotypes. / Pastorelli, R.; Cerri, A.; Rozio, M.; Dell'Omo, M.; Muzi, G.; Abbritti, G.; Fanelli, R.; Airoldi, L.

In: Biomarkers, Vol. 6, No. 5, 2001, p. 357-374.

Research output: Contribution to journalArticle

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abstract = "We investigated whether the presence of (+)-anti-benzo(a)pyrene diolepoxide adducts to serum albumin (BPDE-SA) among workers exposed to benzo(a)pyrene (BaP) and unexposed reference controls was influenced by genetic polymorphisms of cytochrome P4501A1 (CYP1A1), microsomal epoxide hydrolase (EHPX), glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), all involved in BaP metabolism. Exposed workers had significantly higher levels of adducts (0.124 ± 0.02 fmol BPT mg-1 SA, mean ± SE) and a higher proportion of detectable adducts (40.3{\%}) than controls (0.051 ± 0.01 fmol BPT mg-1 SA; 16.1{\%}) (p = 0.014 and p = 0.012). Smoking increased adduct levels only in occupationally exposed workers with the GSTM1 deletion (GSTM1 null) (p = 0.034). Smokers from the exposed group had higher adduct levels when they were CYP1A1 *1/*1 wild-type rather than heterozygous and homozygous for the variant alleles (CYP1A1 *1/*2 plus *2/*2) (p = 0.01). The dependence of BPDE-SA adduct levels and frequency on the CYP1A1 *1/*1 genotype was most pronounced in GSTM1-deficient smokers. Exposed workers with GSTM1 null/GSTP1 variant alleles had fewer detectable adducts than those with the GSTM1 null/GSTP1*A wild-type allele, supporting for the first time the recent in vitro finding that GSTP1 variants may be more effective in the detoxification of BPDE than the wild-type allele. Logistic regression analysis indicated that occupational exposure, wild-type CYP1A1*1/*1 allele and the combination of GSTM1 null genotype + EHPX genotypes associated with predicted low enzyme activity were significant predictors of BPDE-SA adducts. Though our findings should be viewed with caution because of the relatively limited size of the population analysed, the interaction between these polymorphic enzymes and BPDE-SA adducts seems to be specific for high exposure and might have an impact on the quantitative risk estimates for exposure to polycyclic aromatic hydrocarbons.",
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AU - Cerri, A.

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AU - Muzi, G.

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AU - Fanelli, R.

AU - Airoldi, L.

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