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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 65 (1993), S. S7 
    ISSN: 1432-1246
    Keywords: DNA-adduct ; Effect-markert ; Exposure-markert ; Protein-adductt ; Sensitivity-marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Biologic markers are familiar tools for monitoring human absorption of, and reaction to, potentially toxic chemicals. The concept of applying biologic markers to the risk assessment process is a natural, but more recent, development and the principles remain to be fully elaborated. Biologic markers may be measurements of exposure, of effects, of genetic or induced sensitivity or of disease. The ideal biologic marker for risk assessment purposes is a quantitative measurement of a chemical, biochemical, functional or morphological change in the system that is initiated by a chemical and which results in pathologic change and overt toxicity. It follows that some understanding of the mechanism of toxicity and of dose-response relationships are pre-requisite for selection of suitable biologic markers for use in risk assessment. Where biologic markers for toxicity are common between mammalian species, extrapolation of data for quantitative risk assessment purposes becomes more reasonable. In the field of carcinogenesis, some DNA and protein adducts have been proposed as biologic markers for assessment of risk associated with exposure to genotoxic carcinogens. However, less progress is evident in relation to other toxic end-points including those for pulmonary, reproductive, immuno- and neuro-toxicity, despite intensive efforts.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0738
    Keywords: Benzo(a)pyrene ; Protein adducts ; Toxicokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A high performance liquid chromatographic technique coupled with fluorometric detection was used to study the disappearance rate of the hemoglobin and albumin adducts of benzo(a)pyrene (BaP) in female Sprague-Dawley rats. The technique was considered adequate based on good recovery (〉80%) of the analyte and satisfactory intra-assay coefficients of variations of 7.8% and 4.2% for hemoglobin and albumin adducts, respectively. The persistence of the adducts was determined in rats injected intravenously with 550 nmol BaP diolepoxide, the electrophilic metabolite of BaP. In a first experiment the isolated protein fractions were directly subjected to mild acid hydrolysis to yield the ultimate analyte, BaP tetrol. In a second experiment these fractions were first digested by proteases in order to liberate any unbound lipophilic BaP tetrol possibly “hidden” in the hydrophobic portions of the protein matrices. It was found that 70–100% of the measured tetrols originated from true adducts. The half-life of the free tetrol was 2.8 and 1.6 days in the hemoglobin and albumin fractions, respectively, compared to 10.7 and 3.6 days for the true adducts. Based on the total amount of tetrols, the mean half-life of the latter in the hemoglobin and albumin fractions determined from the two experiments was 9.0 and 2.7 days, respectively, assuming first order kinetics. The greater persistence of the hemoglobin adduct compared to that of the albumin adduct is coherent with the biological half-life of the intact proteins. However, the observed disappearance profile obtained does not fit with current models of adduct formation and removal.
    Type of Medium: Electronic Resource
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