Pretreatment with 8-methoxypsoralen, a potent human CYP2A6 inhibitor, strongly inhibits lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in female A/J mice.
Pretreatment with 8-methoxypsoralen, a potent human CYP2A6 inhibitor, strongly inhibits lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in female A/J mice.
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发表时间：
2003-11
期刊：
影响因子：
11.2
通讯作者：
Hijiri Takeuchi;K. Saoo;M. Yokohira;M. Ikeda;H. Maeta;Masafumi Miyazaki;H. Yamazaki;T. Kamataki;K. Imaida
中科院分区：
文献类型：
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作者：
Hijiri Takeuchi;K. Saoo;M. Yokohira;M. Ikeda;H. Maeta;Masafumi Miyazaki;H. Yamazaki;T. Kamataki;K. Imaida
人类 CYP2A6 已被认为参与促诱变剂的诱变激活，例如烟草特有的亚硝胺、4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁酮 (NNK)。据报道 Methoxsalen（8-甲氧基补骨脂素）可抑制 CYP2A6。在本研究中，检测了甲氧沙林对 NNK 诱导的雌性 A/J 小鼠肺部肿瘤发生的抑制作用。雌性 A/J 小鼠接受甲氧沙林治疗，剂量为 50 或 12.5 mg/kg 体重，每天通过胃管给药，持续 3 天。最终治疗一小时后，腹腔注射 NNK。剂量为2毫克/小鼠。第一次甲氧沙林治疗后 16 周终止实验，并对肺腺瘤进行分析。甲氧沙林预处理显着降低肿瘤发生率，从 93.8% 降至 16.7% (50 mg/kg) 和 20.0% (12.5 mg/kg)，肿瘤复数从 5.97 降至 0.23 (50 mg/kg) 和 0.25 (12.5 mg/kg) 肿瘤/小鼠。这些结果清楚地表明，甲氧沙林是一种有效的人类 CYP2A6 抑制剂，是一种针对 NNK 诱导的肺部肿瘤发生的强化学预防剂。
Human CYP2A6 has been recognized as being involved in the mutagenic activation of promutagens such as the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Methoxsalen (8-methoxypsoralen) was reported to inhibit CYP2A6. In the present study, the inhibitory effects of methoxsalen on NNK-induced lung tumorigenesis in female A/J mice were examined. Female A/J mice were treated with methoxsalen at doses of 50 or 12.5 mg/kg body weight, given by stomach tube, daily for 3 days. One h after the final treatment, NNK was injected i.p. at a dose of 2 mg/mouse. The experiments were terminated 16 weeks after the first methoxsalen treatment, and lung adenomas were analyzed. Pretreatment of methoxsalen significantly reduced tumor incidence from 93.8% to 16.7% (50 mg/kg) and 20.0% (12.5 mg/kg), and tumor multiplicity from 5.97 to 0.23 (50 mg/kg) and 0.25 (12.5 mg/kg) tumors/mouse. These results clearly demonstrated that methoxsalen, a potent human CYP2A6 inhibitor, is a strong chemopreventive agent against NNK-induction of lung tumorigenesis.