Falk H L
Fed Proc. 1980 Jan;39(1):76-80.
Extrapolation of bioassay data from high to low doses and from laboratory animal to the human is essential for future growth of the chemical industries and the safeguard of human health and th environment. To be effective this process requires a solid data base: Metabolism of the chemicals holds many clues regarding their carcinogenic hazards, and studies in liver, kidney, and the specific target organs and their cellular organelles are needed. Other environmental chemicals may alter the effects of a single pollutant by enzyme induction or inhibition in liver or target organ (in cytosol, endoplasmic reticulum, or nuclear membranes) and may cause shunts to alternate pathways which must be explored at different dose levels. DNA repair needs further exploration with attention to the molecular location of attachment of the electrophile to DNA bases and the ability of the target cell for effective repair. Inhibition of DNA repair by environmental chemicals needs better understanding. The synergistic effects of chemicals contribute to the complexity of proper extrapolation of data. Cocardinogenicity is not a laboratory curiosity but a real-life situation. Specific human genetic defects involving DNA repair or immunologic competence may further complicate the issues and need exploration.
将生物测定数据从高剂量外推至低剂量，以及从实验动物外推至人类，对于化学工业的未来发展以及人类健康和环境保护至关重要。为使这一过程有效，需要坚实的数据库：化学物质的代谢包含许多有关其致癌危害的线索，需要对肝脏、肾脏、特定靶器官及其细胞器进行研究。其他环境化学物质可能通过肝脏或靶器官（胞质溶胶、内质网或核膜）中的酶诱导或抑制作用改变单一污染物的影响，并可能导致转向替代途径，这必须在不同剂量水平下进行探索。DNA修复需要进一步研究，关注亲电试剂与DNA碱基结合的分子位置以及靶细胞进行有效修复的能力。环境化学物质对DNA修复的抑制作用需要更好地理解。化学物质的协同作用增加了数据正确外推的复杂性。共致癌性并非实验室中的奇闻，而是现实生活中的情况。涉及DNA修复或免疫能力的特定人类遗传缺陷可能使问题更加复杂，需要进行探索。
