Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype

Abstract

Levels of aromatic DNA adducts in foundry workers and controls were followed at four annual samplings. During this time exposure to polycyclic aromatic hydrocarbons (PAH) decreased and the level of DNA adducts decreased accordingly. In the total group exposure was related to the level of adducts. Adduct levels correlated with urinary 1-hydroxypyrene (LOGU1OH), air benzo[a]pyrene, weekly working hours and daily cigarette consumption. In a multivariate model 1-hydroxypyrene had a consistent effect. Neither glutathione transferase M1 (GSTM1) nor cytochrome P450 1A1 (CYP1A1) genotypes had clear effects. Yet the individuals lacking GSTM1 had a stronger effect of LOGU1OH and some effect by other sources of PAH, such as charcoal broiled food, although all these variables were not significant in the multivariate model. The rare individuals with a CYP1A1 polymorphism MspI containing an amino acid change at isoleucine had an increased level of adducts. The results showed that the postlabelling method used was able to detect an increase in aromatic DNA adducts in leukocytes when exposure to benzo[a]pyrene in air was approximately 5 ng/m3. At such low levels smoking and charcoal broiled food may be important contributors to adducts.

Cytochrome P450 (CYP) and glutathione S-transferases (GST) polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1) and urinary levels of 1-hydroxypyrene in Turkish coke oven workers

“…The saturation of enzymes may be a reason for this reverse relationship (Vineis and Martone, 1995;Garte et al, 1997). This is supported by Merlo et al (1998) who found a significant correlation between CYP1A1 Msp1 and 1-OHP excretion at low levels of exposure to PAHs and by Hemminki et al (1997) who showed a significant increase of DNA-adducts at low levels of PAH exposure, similar findings having been reported by Georgiadis et al (2001). The results for our low PAH exposure group, the controls, were in good agreement with the results reported by the aforementioned authors.…”

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.

“…We have previously reported a lack of association between DNA adducts and urinary 1-HOP in garage workers exposed to automobile exhaust (38), but the adduct level correlated with urinary 1-HOP in foundry workers (31). Similarly, as in our observation for DNA adducts, we did not observe any correlation between urinary 1-HOP and the PAH-albumin adduct level.…”

“…In contrast, no difference in DNA adduct level could be observed in street vendors in Milan, Italy, working in areas of high and low traffic density (30). However, the Italian study included both smokers and nonsmokers, and smoking is known to increase the adduct level (31). In the present study an interesting effect of the PMBC composition was observed, as individuals with a high content of B lymphocytes had a lower DNA adduct level.…”

Genotoxic exposures of potroom workers

“…A similar discrepancy in DNA adduct results has been found also for coke workers extensively exposed to PAH. The levels of PAH in foundries and bus garages have been much lower than for potroom workers, but increased DNA adduct levels have nevertheless been observed (33). Variation in the size distribution of the inhaled particles may be a contributing factor to these apparently contradictory findings.…”