Journal of the American College of Toxicology最新文献

{"title":"Mechanisms of Psoralen Action in the Skin.","authors":"Jeffrey D Laskin","doi":"10.3109/10915818909018037","DOIUrl":"10.3109/10915818909018037","url":null,"abstract":"<p><p>The combination of psoralens and ultraviolet light (UVA, 320-400 nm), also referred to as PUVA, is a potent modulator of epidermal cell growth and differentiation. Although it has been postulated that PUVA exerts its actions by binding to DNA, our laboratory has obtained evidence that a specific, saturable, high-affinity receptor site independent of the DNA mediates the biologic actions of these drugs. This receptor is a 22,000 molecular weight protein present in membrane and cytoplasmic fractions of responsive cell types. Treatment of cells with psoralens followed by UV light causes activation of the receptor. This leads to specific cell surface membrane alterations, in particular phosphorylation of the receptor for epidermal growth factor (EGF). The EGF receptor is a transmembrane glycoprotein possessing intrinsic tyrosine kinase activity. Modification of the EGF receptor leads to a loss in its ability to bind EGF, as well as an inhibition of its tyrosine kinase activity. These data indicate that the psoralens act at the level of the cell membrane and that their biologic effects in the skin may be mediated by the ability of these drugs to disrupt normal growth factor functions.</p>","PeriodicalId":73969,"journal":{"name":"Journal of the American College of Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1989-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10915818909018037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9753658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Summary and Perspectives: Panel Discussion on Toxicology and Exposure Assessment: State of the Art","authors":"J. Fowle","doi":"10.3109/10915818909018047","DOIUrl":"https://doi.org/10.3109/10915818909018047","url":null,"abstract":"XPOSURE ASSESSMENT IS THE PROCESS of measuring or estimating the magnitude, frequency, E duration, and route of contact with a chemical or physical agent in the environment. Exposure assessment is part of an overall risk analysis process used by governmental and industrial organizations to decide whether various activities associated with potentially hazardous materials pose a threat to human health or the environment. (Figure 1). Although exposure assessment relies on hazard identification, it must be coupled with additional information to characterize the hazard or risk in order to gain a perspective above the significance of the exposure. Uncertainties associated with current methodologies prevent the precise identification of specific environmental and individual exposures, as well as actual intake of substances and subsequent adverse health effects. Given the present state of knowledge about interspecies extrapolation of toxic effects, it appears that major reductions in the uncertainties associated with risk assessment that are likely to be achieved in the near future will be due to improvements in our ability to estimate exposure to chemicals. This symposium reviewed the strength of techniques now available to estimate exposure and discussed what can be done in the future to improve assessment. The presentations in this symposium addressed three generic questions (Table 1). What are we exposed to? (LaGrone and Wallace); How do we estimate exposure to body tissues? (Wogan, Weston et al., Dunn); and What is the link between exposure and disease? (Chapman et al. and Anton-Culver and Burg). The state of the art of exposure measurements and recommendations to improve the science and utility of exposure assessment were discussed. Several themes were identified, including the need to improve methodology, conduct basic research, collect health surveillance data, understand the effects of multiple exposures to pollutants, collaborate among scientific disciplines, and strengthen community education and community relations efforts concerning the public’s exposure to chemicals.","PeriodicalId":73969,"journal":{"name":"Journal of the American College of Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1989-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10915818909018047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69588344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}