Cho Elizabeth, Li Wan-Ju
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Birth Defects Res C Embryo Today. 2007 Mar;81(1):20-40. doi: 10.1002/bdrc.20088.
Risk assessment derives its confidence from toxicology research that is based on relevancy to human health. This article focuses on two highly topical areas of current scientific research, stem cells and chromatin biology, which present new avenues for preclinical and clinical applications, and the frontier role of tissue engineering and regeneration. Appreciating the utility and necessity of chromatin and human somatic stem cells as research tools and looking toward tissue engineering may close the uncertainty gaps between animal and human cross-species toxicology evaluations. The focus will be on developmental toxicology applications, but appropriate extrapolation to any other areas of toxicology can be made. We further provide background on basic biology of these three areas and examples of how early life exposure to known and potential environmental toxicants induce malformations, childhood and adult-onset diseases, through aberrant chromatin modification of critical gene expressions (acute lymphocyte leukemia, heavy-metal nickel and cadmium-associated defects, and reproductive tract malformations and carcinomas induced by the synthetic estrogen, diethylstilbestrol).
风险评估的可信度源于基于与人类健康相关性的毒理学研究。本文聚焦于当前科学研究中两个热门领域，即干细胞和染色质生物学，它们为临床前和临床应用提供了新途径，以及组织工程与再生的前沿作用。认识到染色质和人类体细胞干细胞作为研究工具的实用性和必要性，并展望组织工程，可能会缩小动物和人类跨物种毒理学评估之间的不确定性差距。重点将放在发育毒理学应用上，但也可适当地外推到毒理学的任何其他领域。我们还提供了这三个领域的基础生物学背景，以及早期生命暴露于已知和潜在环境毒物如何通过关键基因表达的异常染色质修饰（急性淋巴细胞白血病、重金属镍和镉相关缺陷，以及合成雌激素己烯雌酚诱导的生殖道畸形和癌症）导致畸形、儿童期和成人期疾病的例子。
