Djuric Z, Heilbrun L K, Simon M S, Smith D, Luongo D A, LoRusso P M, Martino S
The Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
Cancer. 1996 Feb 15;77(4):691-6.
Oxidative DNA damage can result from numerous endogenous metabolic processes as well as from exposure to environmental and dietary oxidants. One important type of oxidative DNA damage is the formation of hydroxylated DNA bases. This type of DNA damage may have a role in carcinogenesis.
We examined the levels of a hydroxylated thymine residue, 5-hydroxy-methyl-2'-deoxyuridine, in DNA obtained from the peripheral blood of breast cancer patients and control women. The isolated DNA was analyzed for levels of 5-hydroxymethyl-2'-deoxyuridine by gas chromatography with mass spectral detection.
The levels of this modified base were significantly higher in 25 breast cancer patients compared with 38 controls, with levels of 0.112 +/- 0.046 in the cancer patients versus 0.083 - 0.025 in the controls, given as pg 5-hydroxymethyl-2'-deoxyuridine/ng thymidine, mean +/- standard deviation (P = 0.019). After controlling for various covariates, the adjusted mean levels of oxidative DNA damage were still significantly higher in women with breast cancer relative to controls.
These results indicate that the levels of 5-hydroxymethyl-2'-deoxyuridine in DNA from peripheral nucleated blood may be potentially useful as a marker of breast cancer.
氧化DNA损伤可源于多种内源性代谢过程以及暴露于环境和饮食中的氧化剂。氧化DNA损伤的一种重要类型是羟基化DNA碱基的形成。这种类型的DNA损伤可能在致癌过程中起作用。
我们检测了乳腺癌患者和对照女性外周血DNA中羟基化胸腺嘧啶残基5-羟甲基-2'-脱氧尿苷的水平。通过气相色谱-质谱检测分析分离出的DNA中5-羟甲基-2'-脱氧尿苷的水平。
25例乳腺癌患者中这种修饰碱基的水平显著高于38例对照,癌症患者的水平为0.112±0.046,对照为0.083 - 0.025,单位为pg 5-羟甲基-2'-脱氧尿苷/ng胸苷,均值±标准差(P = 0.019)。在控制各种协变量后,乳腺癌女性相对于对照,氧化DNA损伤的校正平均水平仍然显著更高。
这些结果表明,外周有核血细胞DNA中5-羟甲基-2'-脱氧尿苷的水平可能有潜力作为乳腺癌的一个标志物。