Cox L A
U. S. WEST Advanced Technologies and Cox Associates, Denver, Colorado 80128.
Risk Anal. 1991 Sep;11(3):453-64. doi: 10.1111/j.1539-6924.1991.tb00631.x.
Benzene is one of the best studied of the known human carcinogens. It causes leukemia in humans and a variety of solid tumors in rats and mice. Decades of research on benzene metabolism, pharmacokinetics, cytotoxicity, genotoxicity, and carcinogenicity in vivo and in vitro are starting to converge on a small set of overlapping hypotheses about the most probable biological mechanisms of benzene toxicity and carcinogenicity. Although there is still room for surprises, it seems likely that the ultimate answer to the mystery of how benzene exerts its multiple effects will consist of elaborations and extensions of one or more of the current hypotheses. This paper reviews benzene health effects and biology, showing how various aspects of metabolism and cytotoxicity fit together with genotoxic and nongenotoxic effects to help explain how benzene may cause cancer. Its goals are: (i) to introduce the qualitative biological background needed for detailed quantitative dose-response modeling of benzene cancer risks; and (ii) to survey a rapidly evolving area of research that shows promise of producing fundamental insights into the mechanisms of toxicity and carcinogenesis for several chemicals--benzene and perhaps phenols, catechols, and other hydroxylated ring hydrocarbons--in the decade ahead.
苯是已知人类致癌物中研究最为深入的物质之一。它会导致人类患白血病，并在大鼠和小鼠身上引发多种实体瘤。数十年来，针对苯在体内外的代谢、药代动力学、细胞毒性、遗传毒性和致癌性的研究，开始聚焦于一小部分关于苯毒性和致癌性最可能的生物学机制的重叠假设。尽管仍有可能出现意外情况，但苯如何产生多种效应这一谜团的最终答案，似乎很可能是对当前一个或多个假设的细化和扩展。本文综述了苯对健康的影响及其生物学特性，展示了代谢和细胞毒性的各个方面如何与遗传毒性和非遗传毒性效应相互配合，以帮助解释苯可能致癌的原因。其目标是：（i）介绍对苯致癌风险进行详细定量剂量反应建模所需的定性生物学背景；（ii）审视一个快速发展的研究领域，该领域有望在未来十年对几种化学物质——苯以及可能的酚类、儿茶酚和其他羟基化环烃——的毒性和致癌机制产生根本性的见解。
