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  • 1
    ISSN: 1432-1335
    Keywords: Benzene ; Risk estimation ; Carcinogenicity ; Genotoxicity ; Metabolism saturation ; Dose-response relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To date, all risk assessment studies on benzene have been based almost exclusively on epidemiological data. We have attempted a more integrated and quantitative evaluation of carcinogenic risk for humans, trying to utilize, in addition to the epidemiological data, all data available, specifically data on metabolism, genotoxicity, and carcinogenicity in small rodents. An integrated evaluation of the globality of the available data seems to suggest a progressive saturation of metabolic capacity both for man and rodents between 10 and 100 ppm. The most susceptible target cells seem to be different in humans (predominant induction of myelogenous leukemia) and small rodents (induction of a wide variety of tumors). Nevertheless, both epidemiological and experimental carcinogenicity data tend to indicate a flattening of the response for the highest dosages, again suggesting a general saturation of mechanisms of metabolic activation, extended to different target tissues. From a quantitative point of view, the data suggest a carcinogenic potency at 10 ppm two to three times higher than that computable by a linear extrapolation from data in the 100 ppm range. These observations are in accord with the recent proposal of the European Economic Community of reducing benzene time-weighted average occupational levels from 10 to 5 ppm.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The expression of steroid receptors and the in vitro responsiveness to steroids were used to investigate the cell heterogeneity of a BALB/c mammary carcinoma cell line (TS/A) by means of its high- and low-metastatic clones previously selected in vitro. All the clones studied contained appreciable levels of receptors for oestrogens and for glucocorticoids. The in vitro responses of clones to 17β-oestradiol were very poor and comparable; conversely, a heterogeneous pattern of responsiveness to glucocorticoids was observed. In the presence of dexamethasone, the in vitro growth of high-metastatic clones was either unaffected or stimulated and dome formation was significantly increased. Dexamethasone treatment of low-metastatic clones caused inhibition of in vitro proliferation and a morphological shift from a fibroblast-like growth pattern towards the epithelial phenotype. One out of the three low-metastatic clones tested acquired the ability to form domes in the presence of dexamethasone, albeit sporadically. The in vitro treatment with dexamethasone significantly increased the lung colonization ability of the two low-metastatic clones studied, whereas no significant effect was observed with high-metastatic clones. Data presented here suggest that TS/A cell line consists of heterogeneous populations with peculiar proliferative and differentiative responses to glucocorticoids.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6822
    Keywords: DCE ; DBE ; covalent binding to DNA ; microsomes ; cytosolic enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Metabolic activation of 1,2-dichloroethane (DCE) and 1,2-dibromoethane (DBE) to forms able to bind covalently with DNA occurs in vitroeither by wat of microsomal or cytosolic pathways. The involvement of these two pathways is variable with respect to species or compound tested. Rat enzymes are generally more efficient than mouse enzymes in bioactivating haloalkanes and DBE is more reactive than DCE. This parallels both the previous report on in vivocomparative interaction and the higher genotoxicity of DBE.
    Type of Medium: Electronic Resource
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