Air Pollution, the Automobile, and Public Health (1988) / Chapter Skim
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Potential Carcinogenic Effects of Polynuclear Aromatic Hydrocarbons and Nitroaromatics in Mobile Source Emissions
Potential Carcinogenic Effects of Polynuclear Aromatic Hydrocarbons and Nitroaromatics in Mobile Source Emissions
Pages 555-578
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HECHT American Health Foundation Historical Perspective and Directions for the Future / 556 Evaluation of Polyaromatic Hydrocarbon and Nitro-Polyaromatic Hydrocarbon Carcinogenicity / 556 Role of Polyaromatic Hydrocarbons as Human Carcinogens / 556 Tumorigenicity of Polyaromatic Hydrocarbons in Laboratory Animals / 558 Modifiers of Polyaromatic Hydrocarbon Carcinogenesis / 561 Carcinogenicity of Nitro-Polyaromatic Hydrocarbons / 562 Metabolic Activation and Detoxification of Polyaromatic Hydrocarbons and Nitro-Polyaromatic Hydrocarbons / 563 Absorption and Distribution upon Inhalation / 563 Benzotaipyrene / 564 Other Polyaromatic Hydrocarbons / 566 Nitro-Polyaromatic Hydrocarbons / 567 Research Problems Relating to the Potential Carcinogenic Effects of Polyaromatic Hydrocarbons and Nitro-Polyaromatic Hydrocarbons in Humans / 568 Individual Dosimetry / 568 Bioassays in Laboratory Animals / 570 Mechanisms of Polyaromatic Hydrocarbon and Nitro-Polyaromatic Hydrocarbon Carcinogenesis / 571 Summary / 572 Summary of Research Recommendations / 573 Air Pollution, the Automobile, and Public Health. (~3 1988 by the Health Effects Institute.
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These exciting developments represent an important frontier in chemical carcinogenesis research, and their application to assessing the health risks of PAHs and nitro-PAHs are a focus of this chapter. Evaluation of Polyaromatic Hydrocarbon and Nitro Polyaromatic Hydrocarbon Carcinogenicity Role of Polyaromatic Hydrocarbons as Human Carcinogens Since the PAHs to which humans are exposed always occur in a mixture of many compounds, some potentially carcinogenic, assessing PAHs as human carcinogens by epidemiologic studies is difficult.
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. Evidence increasingly suggests that passive exposure to tobacco smoke, as in polluted indoor environments, may increase the risk of lung cancer (International Agency for Research on Cancer 1986~.
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of bioassays described below, strongly indicate that PAHs can cause cancer in humans. Tu me rigenicity of Polyaro ma tic Hydrocarbons in Laboratory Animals Figure 1 illustrates the structures of the PAHs commonly detected in exhaust emissions (International Agency for Research on Cancer 1983~.
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or in a suspension in saline (Stinson and Saff~otti 1983~. Squamous cell carcinoma of the trachea and bronchi induced in a high percentage of Syrian golden hamsters given intratracheal instillations of BaP closely resemble human tumors.
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Clear dose/ response relationships for BaP-induced tumor formation have been demonstrated by using the Syrian golden hamster intratracheal instillation model and the mouse skin initiation/promotion protocol. The yield of respiratory tract tumors, tumor latency, and tumor multiplicity related to dose in hamsters treated with BaP and Fe2O3 (Saf
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The most important known environmental tumor promoters are tobacco smoke and diet. The tumor-promoting activity of tobacco smoke and its condensate has been clearly demonstrated in studies using PAHs as initiators in either the mouse skin or the intratracheal instillation models (Hoffmann et al.
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1985~. Carcinogenicity of Nitro Polyaromatic Hydrocarbons Whereas the carcinogenic activities of PAHs have been evaluated extensively, re search on nitro-PAHs is relatively limited.
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78) Metabolic Activation and Detoxification of Polyaromatic Hydrocarbons and Nitro Polyaromatic Hydrocarbons Absorption and Distribution upon Inhalation Clearance of BaP from the respiratory tract is slower when it is associated with particles than when it is in a pure form (Stinson and Saff~otti 1983~.
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DNA adducts are also formed from metabolites other than the dial epoxides, such as the 4,5-epoxide of 9-hydroxy-BaP, and a number of unidentified BaP/DNA adducts are produced in cultured rat mammary cells in vitro and following direct application of BaP to rat mammary glands in vivo (Phillips et al.
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These studies have shown that the basic pattern of BaP metabolism is qualitatively similar in human tissues and in laboratory animal tissues, but major quantitative differences can occur. The formation of DNA adducts via the 7,8-diol-9,10epoxide pathway is regularly observed in human tissues.
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1980~. Other Polyaromatic Hydrocarbons The discovery that 7,8-diol-9,10-epoxide formation is a major activation pathway for BaP (Sims et al.
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Other Nitro-Polyaromatic Hydrocarbons. The position of the nitro group and the nature of the ring system has a major influence on the metabolism of nitroPAHs.
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· Recommendation 1. The structures of the major DNA adducts and protein adducts formed from representative PAHs and nitro-PAHs should be determined in laboratory animals.
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1986; Shugart 1986~. Further studies are required to characterize the DNA adducts and blood protein adducts of the other five compounds.
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The lack of data relating levels of DNA adducts and protein adducts to cancer risk in laboratory animals, under conditions of chronic PAH or nitro-PAH treatment, is probably the most significant gap in our present ability to assess risk in humans, given the fact that methods for making these measurements are becoming available. Recommendation 4.
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Intratracheal instillation bioassays have been performed on only a limited number of PAHs present in mobile source emissions. These studies should be extended at least to some of the more prevalent or carcinogenic components such as anthanthrene, benzo~ghi]
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Rational evaluation of the potential carcinogenic effects of PAHs and nitro-PAHs in humans requires a basic understanding of the major pathways of metabolic activation and detoxification of these compounds in laboratory animals. The most important tumorigenic compounds that require further study for elucidation of these basic pathways include the six listed with Recommendation 1 as well as benzot]
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Similar conclusions can be drawn about nitro-PAHs, but their metabolic activation and detoxification pathways are not very well characterized at Summary of Research Recommendations HIGH PRIORITY Recommendation 1 The structures of the major DNA adducts and protein adducts formed from representative PAHs and nitro-PAHs should be determined in laboratory animals. Recommendation 2 Methods should be developed for determining individual uptake and metabolic activation of representative PAHs and nitro-PAHs.
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1985. The in vitro metabolic activation of nitro polycyclic aromatic hydrocarbons, In: Polycyclic Hydrocarbons and Carcinogenesis (R.
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pyrene dial epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers, Proc.
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1981a. Comparative studies on the tumor-initiating activity and metabolism of methylfluorenes and methylbenzofluorenes, In: Chemical Analysis and Biological Fate: Polynuclear Aromatic Hydrocarbons, Fifth International Symposium (M.
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1983. Experimental respiratory carcinogenesis with polycyclic aromatic hydrocarbons, In: Comparative Respiratory Tract Carcinogenesis (H.
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1985. Carcinogenicity of nitro polycyclic aromatic hydrocarbons in the newborn mouse liver and lung, Proc.
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