CELLULAR UPTAKE OF CARCINOGENS

具体目标是定义细胞摄取的主要机制 血浆脂蛋白中致癌物质的含量。可能存在(A)被动转移 多环芳香烃(PAH)从血浆脂蛋白到 培养的内皮细胞，(B)脂蛋白脂酶依赖的转移 富含甘油三酯的脂蛋白中的多环芳烃对内皮细胞的作用，以及(C) 细胞摄取含有多环芳烃的脂蛋白。总体目标是 确定多环芳烃进入细胞是由热力学控制还是由 脂蛋白修饰和内吞作用的动力学。特定的 假设如下：(1)在细胞表面，脂蛋白脂肪酶起作用 会缩小脂蛋白的大小，改变脂蛋白的组成 表面膜。然后，PAH可以由其中一个或两个 以下机制：(A)通过界面的横向运动 熔合形成的连续体，(B)作为单个分子穿过水溶液 解决方案。(2)低密度脂蛋白和贫甘油三酯中的多环芳烃 残留物通过几个内吞过程被内化。首字母 化学致癌的步骤是将致癌物输送到靶标。 组织。在血浆中，多环芳烃等非极性物质仅限于血浆中。 脂蛋白。多环芳烃的运输作为速率决定因素具有调节作用 一步。对转移机制的评价、对 竞争过程以及多环芳烃和多环芳烃分布的热力学 它们的代谢物是理解 癌变与脂类代谢。

Specific objectives are to define principal mechanisms of cellular uptake of carcinogens in plasma lipoproteins. There may be (a) passive transfer of polynuclear aromatic hydrocarbons (PAH) from plasma lipoproteins to cultured endothelial cells, (b) lipoprotein lipase dependent transfer of PAH in triglyceride-rich lipoproteins to endothelial cells, and (c) cellular uptake of lipoproteins containing PAH. The general objective is to determine if PAH entry into cells is controlled by thermodynamics or by the kinetics of lipoprotein modification and endocytosis. Specific hypotheses are these: (1) At the cell surface, lipoprotein lipase action will reduce lipoprotein size and change the composition of the lipoprotein surface film. PAH may then be transferred by either or both of the following mechanisms: (a) by lateral movement through an interfacial continuum formed by fusion, (b) as individual molecules through the aqueous solution. (2) PAH in low density lipoproteins and in triglyceride-poor remnants are internalized by several endocytotic processes. The initial step of chemical carcinogenesis is delivery of the carcinogen to the target tissue. In plasma, nonpolar substances such as PAH are confined to plasma lipoproteins. Transport of PAH has a regulatory role as a rate determining step. Evaluation of the mechanisms of transfer, of the rates of competitive processes, and of the thermodynamics of distribution of PAH and their metabolites is necessary to understand the relationship of carcinogenesis and lipid metabolism.