[Heme oxygenase 1 expression in foundry workers].
Heme oxygenase 1 (HO-1) catalyses the oxidation of heme to biliverdin, and its expression is induced by oxidative stress. This study was aimed at assessing the role of metabolic polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1, EPHX) in the modulation of HO-1 gene expression in 37 foundry workers. Blood and urine samples were obtained at the beginning (BS) and at the end (ES) of work shift, in February (T1) and June (T2). Urinary 1-hydroxypyrene (1-OHP) was measured as a tracer of PAH exposure. HO-1 gene expression in ES samples normalized to BS values (HO-1 ES/BS) was higher at T2 respect to T1. HO-1 gene induction was related to ES 1-OHP when considering either T2 samples or the combination of the two samplings. HO-1 ES/BS was significantly increased in subjects with at least a mutant allele for GSTP1 as compared to subjects with GSTP1AA genotype (1.23 +/- 0.002 vs 0.88 +/- 0.002, p < 0.05). Only in subjects with at least one vari.nt allele for GSTP1, a positive correlation between HO-1 ET/IT expression and 1-OHP FT levels was observed (r2 = 0.21, p = 0.016). The present study demonstrates a correlation between PAH exposure, as assessed by urinary 1-OHP, and the induction of HO-1 expression. Such a correlation seems to be limited to subjects bearing variant alleles for GSTP1. At the same exposure levels, these subjects showed a greater expression of HO-1 FT as compared to subjects with GSTP1 wild type genotype, possibly due to a higher oxidative stress in the subjects expressing the mutant GSTP1-1 isoform, which could imply a limited scavenging capacity.
Mozzoni
P
P
Universita di Parma, Dipartimento di Clinica Medica, Nefrologia e Scienze della Prevenzione, Parma. paola.mozzoni@unipr.it
De Palma
G
G
Scotti
E
E
Andreoli
R
R
Folesani
G
G
Maninil
P
P
Apostoli
P
P
Mutti
A
A
D000328:Adult; D003627:Data Interpretation, Statistical; D015870:Gene Expression; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016273:Occupational Exposure; D018384:Oxidative Stress; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000032:analysis / Q000378:metabolism*
D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D006419:Heme Oxygenase (Decyclizing); C033146:1-hydroxypyrene