Malins D C, Gunselman S J
Molecular Epidemiology Program, Pacific Northwest Research Foundation, Seattle, WA 98122.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):13038-41. doi: 10.1073/pnas.91.26.13038.
The use of gas chromatography-mass spectrometry with selected ion monitoring (GC-MS/SIM) and Fourier-transform infrared (FT-IR) spectroscopy revealed a remarkable degree of damage in the hepatic DNA of fish exposed to toxic environmental chemicals, compared with controls. The exposed fish, which were neoplasm-free, were part of a population with a high incidence of liver cancer. GC-MS/SIM showed markedly high concentrations of hydroxyl radical-induced ring-opening products (e.g., 2,6-diamino-4-hydroxy-5-formamidopyrimidine) and 8-hydroxy adducts of adenine and guanine (e.g., 8-hydroxyguanine) in the DNA. FT-IR spectroscopy revealed substantial changes in spectral areas, such as those assigned to NH vibrations of nucleotide bases and CO vibrations of deoxyribose. This diverse and extensive damage to DNA provides a perspective of premalignant changes resulting from xenobiotic exposure and a promising basis for predicting cancer risk in animals and humans.
与对照组相比,使用带有选择离子监测的气相色谱 - 质谱联用仪(GC-MS/SIM)和傅里叶变换红外(FT-IR)光谱法发现,暴露于有毒环境化学物质的鱼类肝脏DNA存在显著程度的损伤。这些暴露的鱼没有肿瘤,它们来自肝癌发病率很高的种群。GC-MS/SIM显示DNA中羟基自由基诱导的开环产物(如2,6-二氨基-4-羟基-5-甲酰胺基嘧啶)以及腺嘌呤和鸟嘌呤的8-羟基加合物(如8-羟基鸟嘌呤)的浓度明显很高。FT-IR光谱显示光谱区域有实质性变化,例如那些归因于核苷酸碱基的NH振动和脱氧核糖的CO振动的区域。DNA这种多样且广泛的损伤为异源物质暴露导致的癌前变化提供了一个视角,也为预测动物和人类的癌症风险提供了一个有前景的基础。