The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers.
The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, nitro-PAH adducts to Hb and MN frequency) could be modulated by the genetic metabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven workers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 genotypes by a PCR assay. In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total PAH exposure (urinary levels of 1-hydroxypyrene) both by a stratified analysis and logistic regression modelling. Statistically significant (P = 0.03 and P = 0.01) higher percentages of the more susceptible GSTM1- subjects compared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val individuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between increased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant interaction between PAH exposure and GSTM1-genotype was found for PAH-DNA adducts. No effect of these metabolic genotypes was observed for MN frequency and nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction between PAH exposure and two metabolic genotypes involved in activation (CYP1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.
Brescia
G
G
Dipartimento di Medicina Interna e Medicina Pubblica, Facoltà di Medicina e Chirurgia, Università di Bari, Policlinico, Italy.
Celotti
L
L
Clonfero
E
E
Neumann
G H
GH
Forni
A
A
Foà
V
V
Pisoni
M
M
Ferri
G M
GM
Assennato
G
G
D000328:Adult; D000388:Air / Q000032:analysis; D015415:Biomarkers; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004789:Enzyme Activation; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects* / Q000032:analysis; D012044:Regression Analysis
D015415:Biomarkers; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D007527:Isoenzymes; D011084:Polycyclic Aromatic Hydrocarbons