Li G, Wang C, Xin W, Yin S
Institute of Occupational Medicine Chinese Academy of Preventive Medicine, Beijing, China, USA.
Environ Health Perspect. 1996 Dec;104 Suppl 6(Suppl 6):1337-8. doi: 10.1289/ehp.961041337.
Chemicals combine with DNA, resulting in DNA damage, which could initiate carcinogenesis. To study whether benzene or benzene metabolites bind to DNA, DNA adducts in various tissues and their persistence in leukocytes were examined using the 32P-postlabeling assay. LACA mice were dosed ip with benzene at 500 mg/kg bw twice for 5 days. Two additional spots of DNA adducts are formed in bone marrow cells, liver cells, and peripheral blood compared with control mice. The relative adduct labeling values are 10.39, 11.32, and 13.77 adducts x 10(-8) nucleotides in these tissues, respectively. DNA adducts in blood leukocytes were observed at 1, 4, 7, 14, and 21 days after exposure to benzene, but adduct levels decreased as a function of time. Relative adduct labeling of "adduct B" declined linearly but mildly, while "adduct C" displayed a stepwise decrease. The relative adduct labeling values of both these adducts at day 14 were 50% of those at day 1 after the last treatment. Both adducts were still detectable at day 21 after benzene exposure. These studies demonstrate that benzene could induce DNA adducts in bone marrow, liver, and white blood cells of mice dosed with benzene and that measurement of adducts in white blood cells may be useful as a biomarker to predict carcinogenic risk of benzene to workers exposed to benzene.
化学物质与DNA结合，导致DNA损伤，进而引发致癌作用。为研究苯或苯代谢产物是否与DNA结合，采用32P后标记分析法检测了各种组织中的DNA加合物及其在白细胞中的持久性。给LACA小鼠腹腔注射500 mg/kg体重的苯，连续两次，每次5天。与对照小鼠相比，骨髓细胞、肝细胞和外周血中形成了另外两个DNA加合物斑点。这些组织中相对加合物标记值分别为10.39、11.32和13.77个加合物×10(-8)核苷酸。在接触苯后的第1、4、7、14和21天观察到血白细胞中的DNA加合物，但加合物水平随时间下降。“加合物B”的相对加合物标记呈线性但轻微下降，而“加合物C”呈逐步下降。在最后一次处理后第14天，这两种加合物的相对加合物标记值均为第1天的50%。在苯暴露后第21天，两种加合物仍可检测到。这些研究表明，苯可在给苯小鼠的骨髓、肝脏和白细胞中诱导DNA加合物，并且检测白细胞中的加合物可能作为一种生物标志物，用于预测苯对接触苯的工人的致癌风险。
