Determination of Hemoglobin and Serum Albumin Adducts of Benzo[a]Pyrene by Gas Chromatography-Mass Spectrometry in Humans and Their Relation to Exposure and to other Biological Markers

Abstract

In this study we have examined the relationship of benzo[a]pyrene (B[a]P) exposure with B[a]P-7,8-diol-9,10-epoxide (BPDE) adduct formation in globin and serum albumin (SA). We also have evaluated the relationship of BPDE-globin and -SA adduct formation with urinary 1 -hydroxypyrene ( 1 -OH-pyrene), and bulky DNA adducts in peripheral blood lymphocytes. The study groups consist of male Hungarian garage mechanics (smokers and nonsmokers) exposed to diesel engine exhaust and matched control samples from a blood bank in Budapest. The mean level of BPDEglobin adducts in the garage mechanics (n=15) is 5.914.8 fmoVmg globin (ranging from 0.5 to 19.9 fmol/mg globin) and that in controls (n=15), is 2.4*2.5 fmol/mg globin (ranging from ND to 8.5 fmol BPDE/mg globin). The mean of BPDE-SA in garage mechanics is 0.3650.6 fmol/mg SA (ranging from ND to 2.6 fmol/mg SA) and, in controls it is 0.29i0.3 fmol/mg SA (ranging from ND to 1.3 fmol/mg SA). The results of this study indicate that levels of BPDE-SA adducts are about one order of magnitude lower than levels of globin adducts. The mean of BPDE-globin and -SA adducts in garage mechanics are 2.4-fold (p=0.02) and 1.2-fold @=0.7) higher than I15 I26 A. A. MELIKIAN e t a /those in controls, respectively. Similarly, levels of urinary 1 -0H-pyrene in the exposed group are 2.1 -fold higher than those in controls @=0.03). The correlation coefficients between estimated B[n]P exposure (both ingested and inhaled) and formation of globin adducts and urinary 1-OH-pyrene are ~0 . 4 9 (p=0.06), and r=0.3 1 (p=0.26), respectively. This study suggests that BPDE-globin adducts and urinary 1-OH-pyrene may be better biomarkers of exposure than BPDE-SA adducts.

Adduct levels from benzo[a]pyrenediol epoxide: Relative formation to histidine in serum albumin and to deoxyguanosine in DNA in vitro and in vivo in mice measured by LC/MS–MS methods

“…The findings of much lower level of BPDE-His in SA compared to the BPDE-dG level in DNA is compatible with similar indications in the literature from the quantification of adduct levels by less specific methods. SA adducts measured by GC/MS as tetrols of BPDE released after acid hydrolysis and DNA adducts measured by 32 P-post labelling showed a ratio of SA to DNA adduct levels of 1:250 in a study of garage mechanics (Melikian et al, 1999).…”

Effect of Delivered Dosage of Cigarette Smoke Toxins on the Levels of Urinary Biomarkers of Exposure

“…By contrast, pyrene, which is a dominant compound in the PAH mixture at a concentration of f50 to 270 ng/cigarette in mainstream smoke, is mainly metabolized to the intermediary 1-OH-P, which forms predominantly 1-OH-P-gluc and, to much smaller extent, a sulfate conjugate, all of which are excreted in urine (35). Because the introduction of the urinary 1-OH-P as a biomarker of human PAH exposure, many studies have confirmed that 1-OH-P is a valid and sensitive indicator of PAH exposure (36,37). The correlation between BaP exposure from mainstream cigarette smoke and urinary 1-OH-P in the current study is r = 0.48 (n = 231).…”