Martin E A, Rich K J, White I N, Woods K L, Powles T J, Smith L L
MRC Toxicology Unit, University of Leicester, UK.
Carcinogenesis. 1995 Jul;16(7):1651-4. doi: 10.1093/carcin/16.7.1651.
32P-Postlabelling of DNA extracted from the livers obtained from seven women receiving tamoxifen (20 mg either once or twice daily) was compared with liver DNA from seven individuals not receiving this drug. In all but one of the treated women, tamoxifen and its N-desmethyltamoxifen metabolite could be detected in liver extracts by high performance liquid chromatography; none was detected in control samples. The total level of 32P-postlabelled DNA adducts extracted from the tamoxifen treated women ranged between 18-80 adducts/10(8) nucleotides. The pattern of 32P-postlabelled adducts was not the same as those seen in rats dosed with this drug. There was no significant difference in the level of DNA damage between the tamoxifen treated and control groups. Although only a small number of subjects has so far been examined it appears that women are less susceptible to liver DNA damage caused by tamoxifen than rats.
对从7名接受他莫昔芬治疗（每日20毫克，一次或两次）的女性肝脏中提取的DNA进行32P后标记，并与7名未接受该药物的个体的肝脏DNA进行比较。除一名接受治疗的女性外，在所有接受治疗的女性肝脏提取物中，通过高效液相色谱法均可检测到他莫昔芬及其N-去甲基他莫昔芬代谢物；对照样品中未检测到。从接受他莫昔芬治疗的女性中提取的32P后标记DNA加合物的总水平在18 - 80个加合物/10(8)个核苷酸之间。32P后标记加合物的模式与用该药物给药的大鼠中观察到的不同。他莫昔芬治疗组和对照组之间的DNA损伤水平没有显著差异。尽管到目前为止只检查了少数受试者，但似乎女性比大鼠对他莫昔芬引起的肝脏DNA损伤更不易感。
