Change in the gene expression of hepatic tamoxifen-metabolizing enzymes during the process of tamoxifen-induced hepatocarcinogenesis in female rats
Change in the gene expression of hepatic tamoxifen-metabolizing enzymes during the process of tamoxifen-induced hepatocarcinogenesis in female rats
复制标题
DOI：
10.1093/carcin/23.3.491
复制
发表时间：
2002-03-01
期刊：
影响因子：
4.7
通讯作者：
Degawa, M
中科院分区：
文献类型：
--
作者：
Kasahara, T;Hashiba, M;Degawa, M
采用RT-PCR方法检测雌性Sprague-Dawley大鼠在他莫昔芬诱导肝癌发生过程中他莫昔芬代谢酶基因表达的改变。大鼠给予他莫昔芬（20 mg/kg体/天）治疗52周，而不给予1天、2周和12周治疗，导致肝增厚结节的形成。他莫昔芬治疗2周和12周后，其诱导结节中既负责解毒（n -去甲基化）又负责活化（α -羟化）的CYP3A亚家族酶，尤其是CYP3A1的基因表达增加，而在治疗52周后，其表达恢复到对照水平。负责a-羟他莫昔芬代谢激活的SULT2A亚家族硫转移酶，尤其是HSTa的基因表达降低到一定水平
Altered gene expression of the enzymes responsible for tamoxifen metabolism during the process of tamoxifen-induced hepatocarcinogenesis in female Sprague-Dawley rats was examined by the RT-PCR method. Treatment of rats with tamoxifen (20 mg/kg body/day) for 52 weeks, but not the 1 day, 2 or 12 week treatments, resulted in the formation of the liver hyperplastic nodules. The gene expression of CYP3A subfamily enzymes, especially CYP3A1, responsible for not only detoxification (N-demethylation) but also activation (alpha-hydroxylation) of tamoxifen, was increased by the tamoxifen treatments for 2 and 12 weeks, whereas after the 52 week treatment, the expression in the induced nodules returned to the control level. The gene expression of SULT2A subfamily sulfotransferases, especially HSTa, responsible for metabolic activation of a-hydroxytamoxifen was decreased to a level