Pub Date : 1989-09-01DOI: 10.3109/10915818909018037
Jeffrey D Laskin
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.
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Pub Date : 1989-09-01DOI: 10.3109/10915818909018047
J. Fowle
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.
暴露评估是测量或估计与环境中的化学或物理物质接触的幅度、频率、持续时间和途径的过程。接触评估是政府和工业组织用来确定与潜在危险物质有关的各种活动是否对人类健康或环境构成威胁的总体风险分析过程的一部分。(图1)尽管暴露评估依赖于危害识别，但它必须与其他信息相结合，以表征危害或风险，以便获得高于暴露重要性的观点。与现行方法有关的不确定性妨碍了准确确定具体的环境和个人接触，以及物质的实际摄入量和随后的不利健康影响。鉴于目前对有毒影响的物种间外推的认识状况，似乎在不久的将来可能实现与风险评估有关的不确定性的重大减少将是由于我们估计化学品接触的能力的提高。这次专题讨论会审查了目前可用来估计暴露的技术的强度，并讨论了今后可以做些什么来改进评估。本次研讨会的报告涉及三个一般性问题(表1):我们暴露于什么环境?(拉格隆和华莱士);我们如何评估人体组织的暴露程度?(Wogan, Weston et al.， Dunn);暴露与疾病之间有什么联系?(Chapman et al.和Anton-Culver and Burg)。讨论了辐照测量技术的现状以及提高辐照评估的科学性和实用性的建议。确定了若干主题，包括需要改进方法、开展基础研究、收集健康监测数据、了解多次接触污染物的影响、各科学学科之间的合作以及加强关于公众接触化学品的社区教育和社区关系努力。
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